Version: IB8_1 CHEMISTRYPHOTO
Broschürentitel / Image II
Owed to the growing demand for tailor-made compounds, our portfolio is fine-tuned by our Custom Synthesis Service at Iris Biotech Laboratories. Our skilled scientists offer profound expertise in • de novo route development, • upscaling towards larger scale production, • as well as synthesis optimization for increased efficiency. Examples are the synthesis of rare chiral building blocks, unnatural amino acid derivatives, sophisticated orthogonal protecting groups, heterocycles, building blocks for nucleotides, PEGs and PEG-analogues as well as specific linkers for controlled drug delivery and release.
Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation III
With this guiding theme in mind, Iris Biotech’s mission is to support researchers by supplying • innovative technologies, rare compounds, as well as a broad portfolio on standard consumables, available in flexible quantities from small scale to bulk quantities. To fulfill our dedication “Empowering Peptide Innovation”, we are attending various conferences, symposia, and exhibitions each year. This allows us to remain in direct contact with scientists all over the world, both from academia and industry, to exchange knowledge, and to gather new ideas to tackle your current challenges.
Guided by our dedication to provide competent service, as well as novel substances and latest technologies, Iris Biotech is your trusted partner for the world of peptides, while having strong expertise in associated disciplines. Thus, our portfolio comprises reagents and tools for the synthesis and purification of peptides, e.g. amino acids, resins and solvents but also for related technologies such as Drug Delivery and Linkerology® and Life Sciences.
InnovationPeptideEmpowering
Amino Acids Building Blocks Life Sciences Drug Delivery Reagents Resins Linkerology® Kits
Broschürentitel / Image Peptide PurificationModificationSynthesis,and Linkerology ® and Drug Delivery Life Sciences (Protected) Amino Acids Standards such as Fmoc-D/LAAA and Boc-D/L-AAA, variety of protecting groups (e.g. Pbf, Trt, tBu, Bzl, Acm, Mob, SIT, Phacm, Allocam, Mmt), unusual amino acids, fluorinated derivatives, substituted prolines, arginine analogues Building Blocks Amino alcohols, amino aldehy des, diamines and hydrazines, (pseudoproline) dipeptides, polyamines and spermines, fatty acid derivatives Reagents Coupling reagents, solvents and scavengers, protecting groups Resins Preloaded resins (e.g. based on Trityl, TCP, TentaGel, Methoxy benzhydryl, Merrifield, PAM, Rink, Wang), scavenger resins, hydrazone resins Kits Chromatography-free peptide purification and modification by Peptide Easy Clean (PEC) Linkers for Solid Phase Peptide SynthesisCleavable Linkers Val-Ala based, Val-Cit based, disulfide based, Dde-helping hands Photo-Activatable Linkers Functionalized Linkers Clickable linkers, trifunctional linkers, linkers with maleimide function, cross-linkers, selective N-term acylation and biotinyla tion PROTACs Ligands, linkers & modules Fullerenes & Poly(2-oxazolines) Poly-Amino Acids Poly-Arg, Poly-Glu, Poly-Lys, Poly-Orn, Poly-Sar PEGylation Branched PEGylating reagents, (amino-)PEG-acids, PEG-amines & hydrazides & guanidines, reagents for tingPEG-maleimides,Biotin-PEG-reagents,Click-conjugation,PEG-thiols,otherPEGylareagents Carbohydrates Galactose, Glucose, Maltose, Mannose, Xylose and others Drug SubstratesPeptidesMetabolites&Inhibitors E.g. protein kinase inhibitors, substrates for fusion (Halo/ Snap/Clip)-tagged proteins Natural Products Dyes and Fluorescent Labels E.g. ICG, AMC, DAPI Maillard & Amadori Reaction Products Large portfolio of derivatives useful as standards for food, pharma and cosmetics industry Vitamins Portfolio Overview
Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation V search High Standards Values: sustainability & responsibility • State-of-the-art equipment & latest QualifiedHightechnologiesqualitystandardssuppliers®ular audits Trust, Honesty & Confidentiality Intergenerational business valuing partnerships • Meeting the customer‘s expectations • Integrity towards our customers Our Know-How One-step reactions & complex multi-step synthesis • Scalability from mg to kg quantities • Route scouting Transparency & Documentation Talk to our specialists – customer care • Certificates of analysis & impurity profiling • Analytical and process reports Step-by-Step Analysis • Customer’s demands Process Evaluation • Detailed literature review Synthetic possibilities Strategy Development • Protocol development Method development and Customizedvalidation synthesis Quality Consistency • Identity confirmation Purity verification Your project requires a compound not listed in our portfolio? Get in contact and inquire about our custom synthesis capabilities. Our experienced scientists are excited to accept your synthetic challenge! In such cases, your request undergoes the following stages: Custom Synthesis Our Service Promise All our services are based on high standards, transparency & documentation, trust, honesty & confidentiality, as well as the required know-how.
Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation Table of contents VII 1.PhotochemistryPhotochemistryinPeptide Synthesis and Bioconjugation 1 2. Diazirine Amino Acids for Photo-Crosslinkage in Living Cells 2 3. Photo-Crosslinkers for Various Applications 7 3.1. Photo-Crosslinkers for Various Applications 7 3.2. Tetrafluorophenyl-Azide-based Photo-Crosslinkers 11 4. Photoactivated Self-Cleaving Linkers and Protecting Groups via Trimethyl Lock 14 5. Furfuryl-Alanine for Side Chain Modification and Bioconjugation 17 6. Photocaged Amino Acid Building Blocks 19 7. Photoswitches 23 8. Photocleavable Auxiliary Reagent for Native Chemical Ligation 26 9. Photo-Linker for Solid Phase Synthesis of Peptide Amides and Acids 28 10. Related Products 30 10.1. Fmoc-Phe-Aca- a Cell Internalization Reporter, and further Fluorescent Amino Acid Derivatives 30 10.2. Building Blocks for the SPPS of FRET-based fluorogenic protease substrates 36 Code of Conduct 39 Terms and Conditions of Sales 41 Index 45
Another common application of photochemistry is the labeling or crosslinking of biomolecules in vitro and in vivo. The latter is of particular interest as a photochemical reaction is one of the few chemical transformations that can be selectively initiated in living cells.
Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation Photochemistry 1 .1. Photochemistry in Peptide Synthesis and Bioconjugation
The term photochemistry describes a group of chemical transformations initiated by irradiation with light. Photochemical reactions usually occur at room temperature and normal pressure, and mostly do not require additional reagents or catalysts, with the notable exception of some cases where the presence of a photosensitizer is necessary. Therefore, photochemical transformations are usually orthogonal to classical chemical transformations, a characteristic that renders them a valuable tool for Consequently,chemists.
the applications of photochemistry are numerous. Orthogonality is a trait often sought for in protecting groups and linkers, as it allows for their selective cleavage. Furthermore, photocleavage is a convenient method for selective removal of auxiliaries after their function has been served. The ty pical moiety that is incorporated into protecting groups, linkers and auxiliaries to facilitate light-induced cleavage is an o-nitrobenzyl group, which undergoes a Norrish-type II reaction upon UV-irradiation.
• Probing protein–protein and protein- peptide interac tions by photo-crosslinking (e.g. site-specific incorpora tion of Photo-Lys into glutathione S-transferase allowing covalent crosslinking of the two subunits of the dimeric protein in E. coli)
Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation 2 .2.
Diazirine Amino Acids for Photo-Crosslinkage in Living Cells
H2N CO2H H2N CO2H H2N NH2 CO2H H2N CO2H H2N CO2H H2N HN N N N N O O N N Photo-Leu
• Probing protein- peptide interactions in order to identify cellular targets of peptides of interest Studying protein−drug interactions and identifying new drug targets By comparing results obtained from different proteomic setups (e.g. live cells and cell lysates), more putative targets can be identified. Fig. 1: Diazirine amino acids and their natural counterparts. S Photo-Met Photo-Lys
Met Lys Leu Photo-Pro HN ProCO2H HN CO2H N N H2N CO2H H2N CO2H N N CF3 PhePhoto-Phe
These amino acids are available in Fmoc- as well as Boc-protected versions for their incorporation into synthetic peptides via standard coupling methods. Furthermore, the unprotected diazirine amino acids are also available for incorporation into expressed peptides and proteins by utilizing the appropriate aminoacyl-tRNA synthetase/tRNA pair. A combination of synthetic and recombinant approaches utilizing NCL has been demonstrated as well. Unnatural amino acids are frequently toxic to cells; however, these photo-amino acids are functional and nontoxic, which allows them to be a premium tool for studying mechanisms and interactions in living cells.
Sar-R-V-Y-V-H-P-F125I
Fig. 2: Use of photo-phenylalanine for the identification of angiotensin-II-receptor binding sites; 125I is used as a radiotracer. back to content arrow-up
RN N Sar-R-V-Y-V-H-P-F125I RN N Internalization Live Cell UV irradiation Sar-R-V-Y-V-H-P-F125I R Live Cell noncovalentbinding covalentbound
CO2H
Applications:
Iris Biotech introduces a comprehensive set of photo-cross linking amino acids bearing the diazirine moiety. Irradiation of diazirines with UV light (ca. 350 nm – 360 nm) yields a highly reactive carbene species that can undergo insertions into C-C, CH, O-H and X-H (X = heteroatom) bonds of neigh boring molecules to irreversibly form a covalent bond. The diazirine moiety is the smallest of all photophores, so intro duction of a diazirine-bearing amino acid into a peptide or protein usually does not impair its biological activity. Further advantages of diazirine crosslinkers are their stability at room temperature, as well as their relative stability to nucleophiles, and to both acidic and basic conditions.
Photochemistry Product details Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation3 HAA3100 H-L-Photo-Leucine*HCl acid(S)-2-amino-3-(3-methyl-3H-diazirin-3-yl)propanoichydrochloride H2N (S) OHNNOCAS-No. 851960-91-3 Formula C 5H9 N3 O 2*HCl Mol. weight 143,14*36,45 g/mol BAA3070 Boc-L-Photo-Leucine*DCHA rin-3-yl)propanoic(S)-2-(tert-butoxycarbonylamino)-3-(3-methyl-3H-diaziaciddicyclohexylamine O NH (S) OH O O NN CAS-No. 1000770-97-7 net Formula C10 H17N3 O4*C12H23 N Mol. weight 243,26*181,34 g/mol FAA4590 Fmoc-L-Photo-Leucine mino)-3-(3-methyl-3H-diazirin-3-yl)propanoic(S)-2-(((9H-fluoren-9-yl)methoxy)carbonyla acid O NH (S) OH O O NN CAS-No. 1360651-24-6 Formula C 20 H19 N3 O4 Mol. weight 365,38 g/mol HAA3110 H-L-Photo-Lysine*HCl carbonylamino)hexanoic(S)-2-amino-6-((2-(3-methyl-3H-diazirin-3-yl)ethoxy)acidhydrochloride OH(S) O HNH2N O O NN CAS-No. 1253643-88-7 Formula C11H20 N4O4*HCl Mol. weight 272,30*36,45 g/mol FAA4600 Fmoc-L-Photo-Lysine hexanoic((2-(3-methyl-3H-diazirin-3-yl)ethoxy)carbonylamino)(S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-6-acid OH(S) O NH HN O O O O NN CAS-No. 2250437-42-2 Formula C 26 H30 N4O 6 Mol. weight 494,54 g/mol BAA3080 Boc-L-Photo-Lysine diazirin-3-yl)ethoxy)carbonylamino)hexanoic(S)-2-(tert-butoxycarbonylamino)-6-((2-(3-methyl-3H-acid OH(S) O NH HN O O O O NN CAS-No. 1330088-06-6 Formula C16 H28 N4O 6 Mol. weight 372,42 g/mol
Product details Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation 4 HAA3120 H-L-Photo-Methionine*HCl (S)-2-amino-4-(3-methyl-3H-diazirin-3-yl)butanoic acid hydrochloride H2N (S) OH O N N CAS-No. 851960-68-4 net Formula C 6 H11N3 O 2*HCl Mol. weight 157,17*36,45 g/mol BAA3090 Boc-L-Photo-Methionine*DCHA zirin-3-yl)butanoic(S)-2-(tert-butoxycarbonylamino)-4-(3-methyl-3H-diaaciddicyclohexylamine NH (S) OH O O O N N CAS-No. 1002754-75-7 net Formula C11H19 N3 O4*C12H23 N Mol. weight 257,29*181,34 g/mol FAA4610 Fmoc-L-Photo-Methionine mino)-4-(3-methyl-3H-diazirin-3-yl)butanoic(S)-2-(((9H-fluoren-9-yl)methoxy)carbonyla acid NH (S) OH O O O N N CAS-No. 945859-89-2 Formula C 21H21N3 O4 Mol. weight 379,41 g/mol HAA3490 H-L-Photo-Phe-OH 4-(trifluoromethyldiazirin)-L-phenylalanine OH (S) O H2N NN F F F CAS-No. 92367-16-3 Formula C11H10 F 3 N3 O 2 Mol. weight 273,21 g/mol BAA1530 Boc-L-Photo-Phe-OH rin)-L-phenylalanineN-alpha-(t-Butyloxycarbonyl)-4-(trifluoromethyldiazi OH (S) O NHO O NN F F F CAS-No. 92367-17-4 Formula C16 H18 F 3 N3 O4 Mol. weight 373,33 g/mol FAA5690 Fmoc-L-Photo-Phe-OH methyldiazirin)-L-phenylalanineN-alpha-(9-Fluorenylmethyloxycarbonyl)-4-(trifluoro OH (S) O NHO O NN F F F CAS-No. 133342-64-0 Formula C 26 H20 F 3 N3 O4 Mol. weight 495,45 g/mol back to content arrow-up
Photochemistry Product details Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation5 HAA3130 H-L-Photo-Proline*HCl (S)-1,2,5-triazaspiro[2.4]hept-1-ene-6-carboxylic acid HN (S) O OHN N CAS-No. 1675206-55-9 Formula C 5H7N3 O 2*HCl Mol. weight 141,13*36,45 g/mol BAA3100 Boc-L-Photo-Proline ene-6-carboxylic(S)-5-(tert-butoxycarbonyl)-1,2,5-triazaspiro[2.4]hept-1-acid O O N (S) O OHN N CAS-No. 1266778-55-5 Formula C10 H15N3 O4 Mol. weight 241,24 g/mol FAA4620 Fmoc-L-Photo-Proline spiro[2.4]hept-1-ene-6-carboxylic(S)-5-(((9H-fluoren-9-yl)methoxy)carbonyl)-1,2,5-triazaacid O O N (S) O OHN N CAS-No. 1266778-58-8 Formula C 20 H17N3 O4 Mol. weight 363,37 g/mol .circle-arrow-right Interested in biotinylation reagents? Check out our corresponding booklet!
Cell-based proteome profiling of potential dasatinib targets by use of affinity-based probes; H. Shi, C. J. Zhang, G. Y. Chen, S. Q. Yao; J Am Chem Soc 2012; 134: 3001-14. https://doi.org/10.1021/ja208518u
Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation 6
References:
https://doi.org/10.1039/c1cc14824a
Proteome profiling reveals potential cellular targets of staurosporine using a clickable cell-permeable probe; H. Shi, X. Cheng, S. K. Sze, S. Q. Yao; Chem Commun (Camb) 2011; 47: 11306-8.
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→ Photo-leucine incorporation reveals the target of a cyclodepsipeptide inhibitor of cotranslational translocation; A. L. MacKinnon, J. L. Garrison, R. S. Hegde, J. Taunton; J Am Chem Soc 2007; 129: 14560-1. https://doi.org/10.1021/ja076250y
https://doi.org/10.1021/ja206661w →
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→ Photo-leucine and photo-methionine allow identification of protein-protein interactions in living cells; M. Suchanek, A. Radzikowska, C. Thiele; Nat Methods 2005; 2: 261-7. https://doi.org/10.1038/nmeth752 back to content arrow-up
→ Synthesis of photoactive analogues of a cystine knot trypsin inhibitor protein; T. Durek, J. Zhang, C. He, S. B. Kent; Org Lett 2007; 9: 5497-500. https://doi.org/10.1021/ol702461z
Probing protein-protein interactions with a genetically encoded photo-crosslinking amino acid; H. W. Ai, W. Shen, A. Sagi, P. R. Chen, P. G. Schultz; Chembiochem 2011; 12: 1854-7. https://doi.org/10.1002/cbic.201100194
Direct interaction between an allosteric agonist pepducin and the chemokine receptor CXCR4; J. M. Janz, Y. Ren, R. Looby, M. A. Kazmi, P. Sachdev, A. Grunbeck, L. Haggis, D. Chinnapen, A. Y. Lin, C. Seibert, T. McMurry, K. E. Carlson, T. W. Muir, S. Hunt, 3rd, T. P. Sakmar; J Am Chem Soc 2011; 133: 15878-81. Aliphatic diazirines as photoaffinity probes for proteins: recent developments; J. Das; Chem Rev 2011; 111: 4405-17. https://doi.org/10.1021/cr1002722 Photo-crosslinking of proteins in intact cells reveals a dimeric structure of cyclooxygenase-2 and an inhibitor-sensitive oligomeric structure of microsomal prostaglandin E2 synthase-1; P. O. Hetu, M. Ouellet, J. P. Falgueyret, C. Ramachandran, J. Robichaud, R. Zamboni, D. Riendeau; Arch. Biochem. Biophys. 2008; 477: 155-62. https://doi.org/10.1016/j.abb.2008.04.038 Covalent capture of phospho-dependent protein oligomerization by site-specific incorporation of a diazirine photo-cross-linker; M. Vila-Perello, M. R. Pratt, F. Tulin, T. W. Muir; J Am Chem Soc 2007; 129: 8068-9. https://doi.org/10.1021/ja072013j
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→ Protein-polymer conjugation via ligand affinity and photoactivation of glutathione S-transferase; E. W. Lin, N. Boehnke, H. D. Maynard; Bioconjug Chem 2014; 25: 1902-9. https://doi.org/10.1021/bc500380r
Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation Photochemistry 7 .3. Photo-Crosslinkers for Various Applications Many photo-crosslinkers for photoaffinity labeling rely on benzophenone as the crosslinking agent. However, these types of crosslinkers usually show low crosslinking yields and require relatively long irradiation times due to slow reaction rates, which may lead to non-specific labeling. Moreover, the irradiation conditions for benzophenones have been shown to lead to cell damage and cell death. Conversely, diazirine- and perfluorophenyl-based crosslinkers generate a reactive species (carbene and nitrene, respectively) upon relatively short irradiation with UV light. Consequently, diazirine- and perfluorophenyl-crosslinkers are commonly used in molecular biology and biochemistry. CR2 R1 N N CR2 R1 OON3NRFF FFFFFF Rhν 260 nm - N2 hν 350 - 360 nm - N2 hν 350 nm Fig. 3: Three types of photophores: Perfluorophenyl azides, diazirines and benzophenones 3.1. Photo-Crosslinkers
Another application of diazirine photo crosslinkers is the surface immobilization of molecules of inte rest. The linker is bound to a surface through its carboxyl or amino functionality, leaving the diazirine group free to react with any type of molecule. Since this reaction takes place irrespective of available functional groups, it is not necessary to chemically modify molecules of interest prior to immobilization. This virtually ensures that molecules are immobilized without altering their binding properties. By using this approach, it is possible to easily create microarrays of whole libraries of small molecules for rapid screening.
Diazirine-bearing crosslinkers are activated at wavelengths that cause little to no damage to cells. In addition to this, trifluoromethylaryl diazirines show a fast initial reaction rate and rapid termination of reaction. Consequently, they exhibit a highly ligand-dependent reactivity, which renders them ideal probes for ligand binding to low-affinity targets, e.g. for probing carbohydrate-lectin interactions.
Moreover, the small size of the diazirine group minimizes the risk of impairing or altering the biological activity of a ligand. Our diazirine crosslinkers are functionalized to react with either carboxyl- or aminereactive ligands, respectively.
Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation 8 R N N alkyl-spacer/ArylSurface R alkyl-spacer/ArylSurface UVpotentialirradiationN2binder potentialbinder R = H or Tfm Fig. 4: Immobilization of molecules of interest on a surface (e.g. a glass slide) using a diazirine crosslinker. R1 R2 N N Aryl- / alkyl-spacerR1=COOH or CH2NH2 R2 = H or Tfm R2 N N Aryl- / alkyl-spacer Probe R2 Aryl- / alkyl-spacer Probe UV irradiationN2 Target coupling to amine- or carboxy-reactive probe Fig. 5: Photoaffinity labeling of a target molecule by a diazirine-functionalized binding probe. Product details RL-2890 Photo-Pentanoic acid 3-(3-methyl-3H-diazirin-3-yl)propanoic acid OH O NN CAS-No. 25055-86-1 Formula C 5H 8 N2O 2 Mol. weight 128,13 g/mol RL-2900 Photo-Hexanoic acid 4-(3-methyl-3H-diazirin-3-yl)butanoic acid OH ONN CAS-No. 16297-97-5 Formula C 6 H10 N2O 2 Mol. weight 142,16 g/mol back to content arrow-up
Photochemistry Product details Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation9 RL-3410 Photo-Click-Heptanoic acid 2-(3-(but-3-ynyl)-3H-diazirin-3-yl)acetic acid OH NN O CAS-No. 2049109-24-0 Formula C 7H 8 N2O 2 Mol. weight 152,15 g/mol RL-3740 Photo-Palmitic acid 9-(3-hexyl-3H-diazirin-3-yl)nonanoic acid OH O NN CAS-No. 2100292-41-7 Formula C16 H30 N2O 2 Mol. weight 282,43 g/mol RL-3720 Photo-Click-Palmitic acid 11-(3-(but-3-yn-1-yl)-3H-diazirin-3-yl)undecanoic acid O OH NNFormula C16 H26 N2O 2 Mol. weight 278,40 g/mol RL-3750 Photo-Stearic acid 11-(3-hexyl-3H-diazirin-3-yl)undecanoic acid OH O NNCAS-No. 1704120-02-4 Formula C18 H34N2O 2 Mol. weight 310,48 g/mol RL-3760 Photo-Click-Stearic acid 13-(3-(but-3-yn-1-yl)-3H-diazirin-3-yl)tridecanoic acid NN O OH Formula C18 H30 N2O 2 Mol. weight 306,45 g/mol RL-2920 Photo-Benzoic acid 4-[3-(Trifluoromethyl)-3H-diazirin-3-yl]benzoic acid F3C N N OHOCAS-No. 85559-46-2 Formula C9 H 5F 3 N2O 2 Mol. weight 230,14 g/mol
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→ Synthesis of Photoactive α-Mannosides and Mannosyl Peptides and Their Evaluation for Lectin Labeling; M. Wiegand, T. K. Lindhorst; Eur. J. Org. Chem. 2006; 2006: 4841-4851. https://doi.org/10.1002/ejoc.200600449 back to content arrow-up
Product details Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation 10 RL-2910 Photo-Butylamine 2-(3-methyl-3H-diazirin-3-yl)ethan-1-amine hydroch loride NH2 NN CAS-No. 25055-95-2 Formula C 4H9 N3*HCl Mol. weight 99,13*36,45 g/mol RL-2930 Photo-Benzylamine*HCl hydrochloride4-[3-(Trifluoromethyl)-3H-diazirin-3-yl]benzylamine F3C N N NH2 CAS-No. 1258874-29-1 Formula C9 H 8 N3 F 3*HCl Mol. weight 215,18*36,45 g/mol References: Reviews: → Hide and seek: Identification and confirmation of small molecule protein targets; A. Ursu, H. Waldmann; Bioorg Med Chem Lett 2015; 25: 3079-86. https://doi.org/10.1016/j.bmcl.2015.06.023 → Development and leading-edge application of innovative photoaffinity labeling; Y. Hatanaka; Chem Pharm Bull (Tokyo) 2015; 63: 1-12. https://doi.org/10.1248/cpb.c14-00645 → Diazirine based photoaffinity labeling; L. Dubinsky, B. P. Krom, M. M. Meijler; Bioorg Med Chem 2012; 20: 554-70. https://doi.org/10.1016/j.bmc.2011.06.066 → Aliphatic diazirines as photoaffinity probes for proteins: recent developments; J. Das; Chem Rev 2011; 111: 4405-17. https://doi.org/10.1021/cr1002722 → Recent Progress in Diazirine-Based Photoaffinity Labeling; M. Hashimoto, Y. Hatanaka; Eur. J. Org. Chem. 2008; 2008: 2513-2523 . https://doi.org/10.1002/ejoc.200701069 → Endeavors to make the photophore, diazirine easy to use; Y. Sadakane; Yakugaku Zasshi 2007; 127: 1693-9. https://doi.org/10.1248/yakushi.127.1693 Photoaffinity labeling: → Comparison of the reactivity of carbohydrate photoaffinity probes with different photoreactive groups; K. Sakurai, S. Ozawa, R. Yamada, T. Yasui, S. Mizuno; Chembiochem 2014; 15: 1399-403. https://doi.org/10.1002/cbic.201402051 → Identification of a substrate-binding site in a peroxisomal beta-oxidation enzyme by photoaffinity labeling with a novel palmitoyl derivative; Y. Kashiwayama, T. Tomohiro, K. Narita, M. Suzumura, T. Glumoff, J. K. Hiltunen, P. P. Van Veldhoven, Y. Hatanaka, T. Imanaka; J Biol Chem 2010; 285: 26315-25. https://doi.org/10.1074/jbc.M110.104547
→ Developing photoactive affinity probes for proteomic profiling: hydroxamate-based probes for metalloproteases; E. W. Chan, S. Chattopadhaya, R. C. Panicker, X. Huang, S. Q. Yao; J Am Chem Soc 2004; 126: 14435-46. https://doi.org/10.1021/ja047044i Insecticidal and neural activities of candidate photoaffinity probes for neonicotinoid binding sites; K. Matsuda, M. Ihara, K. Nishimura, D. B. Sattelle, K. Komai; Biosci Biotechnol Biochem 2001; 65: 1534-41.
https://doi.org/10.1271/bbb.65.1534
→ Grafting Organic and Biomolecules on H-Terminated Porous Silicon from a Diazirine; S. Wei, J. Wang, D.-J. Guo, Y.-Q. Chen, S.-J. Xiao; Chem. Lett. 2006; 35: 1172-1173. https://doi.org/10.1246/cl.2006.1172
→ Immobilization of natural products on glass slides by using a photoaffinity reaction and the detection of protein-small-molecule interactions; N. Kanoh, S. Kumashiro, S. Simizu, Y. Kondoh, S. Hatakeyama, H. Tashiro, H. Osada; Angew. Chem. Int. Ed. 2003; 42: 5584-7. https://doi.org/10.1002/anie.200352164
Photochemistry
Fig. 6: Applications of Tetrafluorophenyl-azides.
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Photoaffinity microarray:
→ A study on photolinkers used for biomolecule attachment to polymer surfaces; D. M. Dankbar, G. Gauglitz; Anal Bioanal Chem 2006; 386: 1967-74. https://doi.org/10.1007/s00216-006-0871-x
→ SPR imaging of photo-cross-linked small-molecule arrays on gold; N. Kanoh, M. Kyo, K. Inamori, A. Ando, A. Asami, A. Nakao, H. Osada; Anal Chem 2006; 78 : 2226-30. https://doi.org/10.1021/ac051777j
3.2. Tetrafluorophenyl-Azide-based Photo-Crosslinkers
Tetrafluorophenyl-azides follow a principle similar to diazirines. Upon irradiation with UV light (ca. 260 nm), a highly stabilized nitrene is formed. Nitrenes are the nitrogen analogs of carbenes (isoelectronic) and react in a comparable fashion. In terms of crosslinking yield and duration of irradi ation, they compare favorably to benzophenones. Moreover, the azido group can also undergo classical copper-catalyzed azide-alkyne cycloadditions. Tetrafluorophenyl-azido crosslinkers are also available with a short PEG-spacer for increased solubility (PEG5000), and as Biotin-TEG-ATFBA (PEG2065) for applications such as surface functionalization with biotin, or the biotinylation of biomacromolecules.
Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation
Product details Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation 12 RL-2035 ATFB 4-Azido-2,3,5,6-tetrafluorobenzoic acid N F FFF OHON+ N CAS-No. 122590-77-6 Formula C 7HF4N3 O 2 Mol. weight 235,1 g/mol RL-2045 ATFB-NHS N-Succinimidyl 4-azido-2,3,5,6-tetrafluorobenzoate N F FFF OON+ N NOOCAS-No. 126695-58-7 Formula C11H4F4N4O4 Mol. weight 332,17 g/mol PEG2065 Biotin-TEG-ATFBA Biotin-triethylenglycol-( p-azido-tetrafluorobenzamide) HN O S NH HN OO O O HN O F F F F NCAS-No. 1264662-85-2 Formula C 27H37F4N7 O 6 S Mol. weight 663,68 g/mol PEG5000 N3 -TFBA-O2Oc ethoxy}acetic{2-[2-(4-Azido-2,3,5,6-tetrafluorobenzoyl-amino)ethoxy]acid N F FFF HNON+ N O O OH O CAS-No. 1993119-45-1 Formula C13 H12F4N4O 5 Mol. weight 380,25 g/mol References: → Tri- and Tetravalent Photoactivable Cross-Linking Agents; A. Welle, F. Billard, J. Marchand-Brynaert; Synthesis 2012; 44: 2249-2254. https://doi.org/doi:10.1055/s-0031-1290444 → Candida albicans biofilm formation on peptide functionalized polydimethylsiloxane; K. De Prijck, N. De Smet, M. Rymarczyk-Machal, G. Van Driessche, B. Devreese, T. Coenye, E. Schacht, H. J. Nelis; Biofouling 2010; 26: 269-75. https://doi.org/10.1080/08927010903501908 → Perfluorophenyl azides: new applications in surface functionalization and nanomaterial synthesis; L. H. Liu, M. Yan; Acc Chem Res 2010; 43: 1434-43. https://doi.org/10.1021/ar100066t
→ Recent Trends in the Evaluation of Photochemical Insertion Characteristics of Heterobifunctional Perfluoroaryl Azide Chelating Agents: Biochemical Implications in Nuclear Medicine; R. S. Pandurangi, S. R. Karra, R. R. Kuntz, W. A. Volkert; Photochem. Photobiol. 1997; 65: 208-221. https://doi.org/10.1111/j.1751-1097.1997.tb08547.x back to content arrow-up
→ Photoreactive insulin derivatives for the detection of the doubly labeled insulin receptor; J. Kleinjung, M. Fabry; Peptides 2000; 21: 401-6.
→ Photo-click immobilization of carbohydrates on polymeric surfaces--a quick method to functionalize surfaces for biomolecular recognition studies; O. Norberg, L. Deng, M. Yan, O. Ramstrom; Bioconjug Chem 2009; 20: 2364-70. https://doi.org/10.1021/bc9003519
https://doi.org/https://doi.org/10.1016/S0196-9781(00)00164-9
Synthesis of a tetrafluoro-substituted aryl azide and its protio analog as photoaffinity labeling reagents for the estrogen receptor; K. G. Pinney, J. A. Katzenellenbogen; J. Org. Chem. 1991; 56: 3125-3133.
→
https://doi.org/10.1021/bc00026a007
→
Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation Photochemistry 13 → Comparison of Phenylcarbene and Phenylnitrene; M. S. Platz; Acc. Chem. Res. 2002; 28 : 487-492.
→
https://doi.org/10.1021/ar00060a004 N-Hydroxysuccinimide Ester Functionalized Perfluorophenyl Azides as Novel Photoactive Heterobifunctional Crosslinking Reagents. The Covalent Immobilization of Biomolecules to Polymer Surfaces; M. Yan, S. X. Cai, M. N. Wybourne, J. F. W. Keana; Bioconjug. Chem. 1994; 5: 151-157.
→
https://doi.org/10.1021/jo00009a037
New reagents for photoaffinity labeling: synthesis and photolysis of functionalized perfluorophenyl azides; J. F. W. Keana, S. X. Cai; J. Org. Chem. 1990; 55: 3640-3647. https://doi.org/10.1021/jo00298a048 Affinity Labelling of Antibodies with Aryl Nitrene as Reactive Group; G. W. J. Fleet, R. R. Porter, J. R. Knowles; Nature 1969; 224: 511-512. https://doi.org/10.1038/224511a0
OH R2 X O R1 O R2 O O R2 X O R1PG hν PG
Iris Biotech introduces a series of self-immolative compounds that find application as protecting groups, linkers, or amino acid derivatives (Spr = stimulus-responsive peptide bond cleaving residue). The selfcleavage is induced by irradiation with UV light (ca. 350 – 365 nm) that leads to the unmasking of a hydroxyl group of a 2-alkyl-3,5-dimethyl phenol moiety. The photocleavable group is either o-nitrobenzyl or o-nitroveratryl, which can be cleaved at wavelengths > 350 nm. Since wavelengths above 350 nm tend to be unproblematic for biomacromolecules, this technique is especially interesting for cell-based Thesystems.liberated OH-group serves as a nucleophile that intramolecularly cleaves ester (or amide) bonds at neutral pH and room temperature by cyclization via a six-membered transition state. This reaction is greatly accelerated since the sterically unfavorable interaction between the methyl group at the 3-po sition of the phenol core and the two geminal CH3-groups on the alkyl chain (in β-position to the ester or amide carbonyl group) favor conformations that bring the phenolic OH-group and the neighboring carbonyl function into closer vicinity. This phenomenon is termed the gem-dialkyl effect, for which a theory was first proposed by Thorpe and Ingold in 1915 (“Thorpe-Ingold effect”). An alternative explanation for this effect was posited by Bruice and Pandit in 1960 (“reactive rotamer effect”). phenol core sterically interactionunfavorable 7: Principle of photoactivated trimethyl lock; PG = o-nitrobenzyl or o-nitroveratryl; X = O or NH; R1 –XH = target molecule; R 2 = H or NH-alkyl. The applications for this approach are numerous. Incorporation of a Spr-residue into a peptide sequence enables the photoactivated self-cleavage of the peptide at the position of said residue. This technique allows for the intracellular removal of e.g. cell penetrating peptides or localization sequences from a bioactive molecule. The Spr-residue can also be used as a photolabile linker in order to reversibly connect a moiety such as biotin to a molecule of interest. Finally, while o-nitroveratryl itself is a valuable protecting group for sulfhydryl groups, the combination of o-Nv with a trimethyl lock moiety also allows for its use as a protecting group for hydroxyl and amino functions. back to content arrow-up
Photoactivated Self-Cleaving Linkers and Protecting Groups via Trimethyl Lock
Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation 14 .4.
H X R1 Fig.
→ The Effect of Geminal Substitution Ring Size and Rotamer Distribution on the Intramolecular Nucleophilic Catalysis of the Hydrolysis of Monophenyl Esters of Dibasic Acids and the Solvolysis of the Intermediate Anhydrides; T. C. Bruice, U. K. Pandit; J. Am. Chem. Soc. 1960; 82: 5858-5865. https://doi.org/10.1021/ja01507a023
→ Design and synthesis of caged ceramide: UV-responsive ceramide releasing system based on UV-induced amide bond cleavage followed by O–N acyl transfer; A. Shigenaga, H. Hirakawa, J. Yamamoto, K. Ogura, M. Denda, K. Yamaguchi, D. Tsuji, K. Itoh, A. Otaka; Tetrahedron 2011; 67: 3984-3990. https://doi.org/10.1016/j.tet.2011.04.048
→ CXIX.—The formation and stability of spiro-compounds. Part I. spiro-Compounds from cyclohexane; R. M. Beesley, C. K. Ingold, J. F. Thorpe; J. Chem. Soc., Trans. 1915; 107: 1080-1106. https://doi.org/10.1039/ct9150701080
→ Development and photo-responsive peptide bond cleavage reaction of two-photon near-infrared excitationresponsive peptide; A. Shigenaga, J. Yamamoto, Y. Sumikawa, T. Furuta, A. Otaka; Tetrahedron Lett. 2010; 51: 2868-2871. https://doi.org/10.1016/j.tetlet.2010.03.079
Photochemistry Product details Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation15 FAA7190 Fmoc-Spr(oNB)-OH alanineta-dimethyl-(2,4-dimethyl-6-(2-nitrobenzyloxy)phenyl)N-alpha-(9-Fluorenylmethyloxycarbonyl)-beta,be(rac.) OH O NHO O O NO2 CAS-No. 1032400-98-8 Formula C 35H34N2O 7 Mol. weight 594,66 g/mol FAA7200 Fmoc-Spr(oNv)-OH (rac.)methyl-(2-methyl-6-(2-nitroveratryl)phenyl)alanineN-alpha-(9-Fluorenylmethyloxycarbonyl)-beta,beta-di OH O NHO O O NO2 MeOMeOCAS-No. 1228829-20-6 Formula C 36 H36 N2O 9 Mol. weight 640,68 g/mol RL-2970 Photo-Trimethyl-Lock ric3-(2-Nitroveratryl-4,6-dimethylphenyl)-3-methylbutyacid O OH O NO2 MeO OMe CAS-No. 2095134-25-9 Formula C 22H27NO 7 Mol. weight 417,45 g/mol References: → Invention of stimulus-responsive peptide-bond-cleaving residue (Spr) and its application to chemical biology tools; A. Shigenaga, J. Yamamoto, T. Kohiki, T. Inokuma, A. Otaka; J. Pept. Sci. 2017; 23: 505-513. https://doi.org/10.1002/psc.2961 → Syntheses and kinetic studies of cyclisation-based self-immolative spacers; S. Huvelle, A. Alouane, T. Le Saux, L. Jullien, F. Schmidt; Org Biomol Chem 2017; 15: 3435-3443. https://doi.org/10.1039/c7ob00121e →
Photo-triggered fluorescent labelling of recombinant proteins in live cells; D. Jung, K. Sato, K. Min, A. Shigenaga, J. Jung, A. Otaka, Y. Kwon; Chem Commun (Camb) 2015; 51: 9670-3.
https://doi.org/10.1039/c5cc01067e →
Trimethyl lock: A trigger for molecular release in chemistry, biology, and pharmacology; M. N. Levine, R. T. Raines; Chem. Sci. 2012; 3: 2412-2420. https://doi.org/10.1039/C2SC20536J
→ gem-disubstituent effect: theoretical basis and synthetic applications; M. E. Jung, G. Piizzi; Chem Rev 2005; 105: 1735-66. https://doi.org/10.1021/cr940337h
Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation 16 .circle-arrow-right Find more linkers and background on Linker Technology in our booklet Linkerology ®! back to content arrow-up
Product
Iris Biotech offers Fmoc-L-Ala(2-Furyl)-OH suitable for SPPS, as well as H-L-Ala(2-Furyl)-OH which can be incorporated into proteins using the amber suppression methodology. details HAA2930 H-L-Ala(2-Furyl)-OH (S) H2N OH CAS-No. 127682-08-0 Mol. weight 155,15 g/mol
A novel and innovative approach is the site-specific labeling using the unnatural amino acid 2-furylalanine. UV-irradiation in the presence of oxygen and a photosensitizer converts furyl-alanine to an unsaturated dicarbonyl compound. This intermediate selectively reacts with certain nucleophiles such as hydrazine derivatives of dyes or fluorescent labels. This reaction can be used for the site-specific labeling of peptides and proteins and can be carried out in aqueous solution. O H2N-NH hν, O2, photosensitizerH2O O H2N-NH hν, O2, H2OH2N COOH H2N COOH H2N COOH photosensitizer Peptide Peptide Peptide 8: Site-specific labeling of peptides and proteins using 2-Furyl-alanine.
OO
Labeling with different tags and reporter groups is a pivotal technique for the elucidation of peptide and protein function.
Furfuryl-Alanine for Side Chain Modification and Bioconjugation
O O
2-Furyl-alanine can be incorporated into peptides via SPPS or by using enzymatic approaches. UV-irra diation in the presence of oxygen and a photosensitizer converts furyl-alanine to an intermediate that selectively reacts with certain nucleophiles. This property can be employed for site-specific labeling of peptides and proteins.
O O
Fig.
Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation Photochemistry 17 .5.
→ Red-light-controlled protein-RNA crosslinking with a genetically encoded furan; M. J. Schmidt, D. Summerer; Angew. Chem. Int. Ed. 2013; 52: 4690-3. https://doi.org/10.1002/anie.201300754 back to content arrow-up
Product details Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation 18 FAA4250 Fmoc-L-Ala(2-Furyl)-OH nyl)-3-(2-furyl)-L-alanineN-alpha-(9-Fluorenylmethyloxycarbo (S) NH OHOOO O CAS-No. 159611-02-6 Formula C 22H19 NO 5 Mol. weight 377,39 g/mol References: → Novel furan-oxidation based site-specific conjugation methodology for peptide labeling and antibody drug conjugates; presented at the 6th World ADC meeting October 19th-22nd 2015, San Diego, CA; An Van Den Bulcke, Eirini Antonatou, Willem Vannecke, Kurt Hoogewijs, Annemieke Madder. → Exploiting furan‘s versatile reactivity in reversible and irreversible orthogonal peptide labeling; K. Hoogewijs, D. Buyst, J. M. Winne, J. C. Martins, A. Madder; Chem Commun (Camb) 2013; 49: 2927-9. https://doi.org/10.1039/c3cc40588e → Sequence specific DNA cross-linking triggered by visible light; M. Op de Beeck, A. Madder; J Am Chem Soc 2012; 134: 10737-40. https://doi.org/10.1021/ja301901p → Unprecedented C-selective interstrand cross-linking through in situ oxidation of furan-modified oligodeoxynucleotides; M. Op de Beeck, A. Madder; J Am Chem Soc 2011; 133: 796-807. https://doi.org/10.1021/ja1048169
→ Bioorthogonal chemistry: fishing for selectivity in a sea of functionality; E. M. Sletten,C. R. Bertozzi; Angew. Chem. Int. Ed. 2009; 48: 6974-98. https://doi.org/10.1002/anie.200900942
→
→ Structural basis of furan-amino acid recognition by a polyspecific aminoacyl-tRNA-synthetase and its genetic encoding in human cells; M. J. Schmidt, A. Weber, M. Pott, W. Welte, D. Summerer; Chembiochem 2014; 15: 1755-60. https://doi.org/10.1002/cbic.201402006
Furan-modified oligonucleotides for fast, high-yielding and site-selective DNA inter-strand cross-linking with non-modified complements; K. Stevens, A. Madder; Nucleic Acids Res 2009; 37: 1555-65. https://doi.org/10.1093/nar/gkn1077
→ From DNA cross-linking to peptide labeling: on the versatility of the furan-oxidation-conjugation strategy; A. Deceuninck, A. Madder; Chem Commun (Camb) 2009; 340-2 https://doi.org/10.1039/b817447d
Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation Photochemistry 19 .6. Photocaged Amino Acid Building Blocks
OMe O2N OMe S OH O FmocHN N O2N S S Peptide FmocHN OH O N O2N S S hν SPPS Peptide SH N O2N S S MeO MeONO2 S Peptide S S AcmS AcmS
AcmS
A common modification to the ortho-nitrobenzyl motif is the addition of two methoxy groups to the phenyl ring. The resulting ortho-nitroveratryl (oNv) group is compatible with SPPS protocols and can be cleaved by irradiation with UV light (350 nm) under ambient conditions.
One possible application of the oNv PG is the regiospecific formation of disulfide bonds. When combined with S-pyridinesulfenyl activation by employing Fmoc-L-Cys(Npys)-OH (FAA1975), the Fmoc-L-Cys(oNv)-OH (FAA3970) building block allows for a rapid in situ SS-bond formation. The versatility of this approach was demonstrated by applying it in the synthesis of a number of model peptides such as oxytocin, alpha-conotoxin ImI, and human insulin. SAcm SAcm SAcm Fig. 9: Selective deprotection of 2-nitroveratryl in the presence of other cysteine protecting groups, and subsequent disulfide bond formation with an Npys-functionalized cysteine.
The oNv group can also be employed to protect the side chain of lysine if it is used as the corresponding oxycarbonyl derivative, abbrevia ted Nvoc (o-nitroveratryloxycarbonyl). The corresponding building block Fmoc-L-Lys(Nvoc)-OH (FAA7230) is available at Iris Biotech. Additionally, o-nitroveratryl may be used as a solubilizing tag on the alpha-amino group of glycine for internal solubilization, which can be cleaved by photolysis (350 nm) under ambient conditions.
Photocaged amino acids offer a mild and selective way to deprotect reactive side-chain functional groups such as amines or thiols, thus adding another level of orthogonality to the peptide chemist’s toolbox. Photolabile protecting groups (PGs) are frequently based on the ortho-nitrobenzyl moiety or variations thereof. Upon irradiation with UV light, such nitrobenzyl-based PGs undergo a Norrish type II reaction, liberating the protected functional group.
Another variation of the o-nitrobenzyl motif is the nitrodibenzofuran (NDBF) group that has an additio nal benzofuran ring system fused to the existing phenyl ring. NDBF is a one- and two-photon sensitive protecting group for cysteine. Analogous to the oNv group, NDBF can also be used to protect the epsilon amino group of lysine in the form of the corresponding oxycarbonyl derivative NDBFOC. Both Fmoc-LCys(NDBF)-OH (FAA8420) and Fmoc-L-Lys(NDBFOC)-OH (FAA8425) are available at Iris Biotech as readyto-use building blocks for peptide synthesis. Selective deprotection by photolysis is achieved either by irradiation with UV light (365 nm), or by two-photon excitation with near-infrared (800 nm) light. The latter aspect renders this derivative particularly useful for biological applications in live cells or intact organisms due to the increased penetration depth of NIR light, as well as its biocompatibility. In addition, this cage exhibits a faster UV photolysis rate relative to simple nitroveratryl derivatives. An example showed that NDBF is photolyzed 16–160 times more efficiently than other nitrobenzyl PPGs. Further variations include the dimethoxynitrobenzyl group, as well as the methyl-o-nitropiperonyl group, which are used to protect selenocysteine and cysteine, respectively. Fmoc-L-Cys(oNv)-OH atryl)-L-cysteineN-alpha-(9-Fluorenylmethyloxycarbonyl)-S-(2-nitrover
Product details FAA3970
OH(R) O NHO O SO2N OMeOMe CAS-No. 214633-71-3 Formula C 27H26 N2O 8 S Mol. weight 538,57 g/mol FAA1975 Fmoc-L-Cys(Npys)-OH nyl)-S-(3-nitro-2-pyridylthio)-L-cysteineN-alpha-(9-Fluorenylmethyloxycarbo OH(R) O NHO O S S N O2N Formula C 23 H19 N3 O 6 S 2 Mol. weight 497,54 g/mol FAA5660 Fmoc-D-Cys(Npys)-OH nyl)-S-(3-nitro-2-pyridylthio)-D-cysteineN-alpha-(9-Fluorenylmethyloxycarbo OH(S) O NHO O S S N O2N Formula C 23 H19 N3 O 6 S 2 Mol. weight 497,54 g/mol FAA7230 Fmoc-L-Lys(Nvoc)-OH lon-(o-nitroveratryloxycarbonyl)-L-lysineN-alpha-(9-Fluorenylmethyloxycarbonyl)-N-epsi OH (S) O NH O O O HNO NO2 OMe OMe CAS-No. 150571-28-1 Formula C 31H33 N3 O 10 Mol. weight 607,61 g/mol back to content arrow-up
Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation 20
Photochemistry Product details Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation21 FAA8420 Fmoc-L-Cys(NDBF)-OH nyl)-S-(1-(3-nitro-dibenzofuran-2-yl)-ethyl)-L-cysteineN-alpha-(9-Fluorenylmethyloxycarbo HN S O ONO2OH O O CAS-No. 1895883-28-9 Formula C 32H26 N2O 7S Mol. weight 582,62 g/mol FAA8425 Fmoc-L-Lys(NDBFOC)-OH nyl)-L-lysinelon-(1-(3-nitro-dibenzofuran-2-yl)-ethoxycarboN-alpha-(9-Fluorenylmethyloxycarbonyl)-N-epsi HN OH O O O HN O NO2 O O Formula C 36 H33 N3 O 9 Mol. weight 651,66 g/mol HAA9255 H-L-Sec(DMNB)-OH*TFA Dimethoxynitrobenzyl selenocysteine TFA salt H2N OHOSe O2N OOCAS-No. 1644398-13-9 Formula C12H16 N2O 6 Se*CF 3 COOH Mol. weight 363,24*114,02 g/mol HAA9320 H-L-Cys(DMNB)-OH Dimethoxynitrobenzyl cysteine OOO2NS H2N OH O CAS-No. 214633-68-8 Formula C12H16 N2O 6 S Mol. weight 316,33 g/mol HAA9270 H-L-Cys(MDNPE)-OH teine1-[4‘,5‘-(methylenedioxy)-2‘-nitrophenyl]ethyl]-L-cys OON O OS (R)H2N OH O CAS-No. 1551078-43-3 Formula C12H14N2O 6 S Mol. weight 314,31 g/mol FAA7350 Fmoc-N(oNv)-Gly-OH N-alpha pha-(o-nitroveratryl)-glycine(9-Fluorenylmethyloxycarbonyl)-N-al O N OH O O MeOMeO NO2 CAS-No. 850859-64-2 Formula C 26 H24N2O 8 Mol. weight 492,48 g/mol
→ Synthesis, stability and optimized photolytic cleavage of 4-methoxy-2-nitrobenzyl backbone-protected peptides; E. C. B. Johnson, S. B. H. Kent; Chem. Commun. 2006; 1557-1559 https://doi.org/10.1039/B600304D
→ A red shifted two-photon-only caging group for three-dimensional photorelease. Y. Becker, E. Unger, M. A. H. Fichte, D. A. Gacek, A. Dreuw, J. Wachtveitl, P. J. Walla, A. Heckel; Chem. Sci. 2018; 9: 2797-2902. https://doi.org/10.1039/c7sc05182d.
→ Production of selenoproteins (selprot); S. Klimašauskas, R. Rakauskaité, V. Masevičiusab; WO2015005756A1. back to content arrow-up
→ Biosynthetic selenoproteins with genetically-encoded photocaged selenocysteines; R. Rakauskaité, G. Urbanavičiūtė, A. Rukšėnaitė, Z. Liutkevičiūtė, R. Juškėnas, V. Masevičiusab, S. Klimašauskas; Chem. Commun. 2015; 51: 8245-8248. https://doi.org/10.1039/C4CC07910H.
→ The nitrodibenzofuran chromophore: a new caging group for ulta-efficient photolysis in living cells. A. Momotake, N. Lindegger, E. Niggli, R. J. Barsotti, G. C. R. Ellis-Davies; Nat. Methods 2006; 3: 35-40. https://doi.org/10.1038/NMETH821.
→ Photomodulation of Protein Trans-Splicing Through Backbone Photocaging of the DnaE Split Intein; L. Berrade, Y. Kwon, J. A. Camarero; Chembiochem 2010; 11: 1368-1372. https://doi.org/10.1002/cbic.201000157
→ Nitrodibenzofuran: A One- and Two-Photon Sensitive Protecting Group That Is Superior to Brominated Hydroxycoumarin for Thiol Caging in Peptides. M. M. Mahmoodi, D. Abate-Pella, T. J. Pundsack, C. C. Palsuledesai, P. C. Goff, D. A. Blank, M. D. Distefano; J. Am. Chem. Soc. 2016; 138: 5848-5859. https://doi.org/10.1021/jacs.5b11759.
Product details Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation 22 FAA7200 Fmoc-Spr(oNv)-OH (rac.)methyl-(2-methyl-6-(2-nitroveratryl)phenyl)alanineN-alpha-(9-Fluorenylmethyloxycarbonyl)-beta,beta-di OH O NHO O O NO2 MeOMeOCAS-No. 1228829-20-6 Formula C 36 H36 N2O 9 Mol. weight 640,68 g/mol RL-2970 Photo-Trimethyl-Lock ric3-(2-Nitroveratryl-4,6-dimethylphenyl)-3-methylbutyacid O OH O NO2 MeO OMe CAS-No. 2095134-25-9 Formula C 22H27NO 7 Mol. weight 417,45 g/mol References: → Total chemical synthesis of photoactivatable proteins for light-controlled manipulation of antigen–antibody interactions; S. Tang, Z. Wan, Y. Gao, J.-S. Zheng, J. Wang, Y.-Y. Si, X. Chen, H. Qi, L. Liu, W. Liu; Chem. Sci. 2016; 7: 1891-1895. https://doi.org/10.1039/C5SC03404C → 2-Nitroveratryl as a Photocleavable Thiol-Protecting Group for Directed Disulfide Bond Formation in the Chemical Synthesis of Insulin; J. A. Karas, D. B. Scanlon, B. E. Forbes, I. Vetter, R. J. Lewis, J. Gardiner, F. Separovic, J. D. Wade, M. A. Hossain; Chemistry 2014; 20: 9549-9552. https://doi.org/10.1002/chem.201403574
→ Design and Synthesis of Photochemically Controllable Restriction Endonuclease BamHI by Manipulating the Salt-Bridge Network in the Dimer Interface; M. Endo, K. Nakayama, T. Majima; J. Org. Chem. 2004; 69: 4292-4298. https://doi.org/10.1021/jo035774n
→ Methoxy-Substituted Nitrodibenzofuran-Based Protecting Group with an Improved Two-Photon Action Cross-Section for Thiol Protection in Solid Phase Peptide Synthesis. T. K. Bader, F. Xu, M. H. Hodny, D. A. Blank, M. D. Distefano; J. Org. Chem. 2020; 85: 1614-1625. https://doi.org/10.1021/acs.joc.9b02751.
→ Genetic Encoding of Photocaged Cysteine Allows Photoactivation of TEV Protease in Live Mammalian Cells; D. P. Nguyen, M. Mahesh, S. J. Elsässer, S. M. Hancock, C. Uttamapinant, J. W. Chin; J. Am. Chem. Soc. 2014; 136(6) : 2240-2243. https://doi.org/10.1021/ja412191m.
The most common motif that is used in this approach is the azobenzene moiety, owing to the large geometrical change that results from adopting a different configuration. Azobenzene-based photoresponsive systems have also been successfully applied in several biological systems. The azobenzene moiety is synthetically accessible via various pathways (Mills reaction, oxidative/reductive coupling, azo coupling), and its photochromic properties can easily be finetuned. The thermodynamically more stable trans isomer adopts an extended planar configuration with a dipole moment close to zero, while the higher energy, metastable cis isomer is more polar and exhibits unfavorable steric interactions. H (S) O H N N N O N H (S) O 10: Interconversion between the trans- and cis-isomers of the diazobenzene motif in a photoswitchable peptide.
Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation Photochemistry 23 .7. Photoswitches
An additional benefit of the azobenzene motif is its high degree of reversibility. It can undergo approxi mately 100 switching cycles without detectable photodegradation or loss of responsiveness. However, although the trans isomer can be regenerated 100% by thermal relaxation, full conversion of one or the other isomer by irradiation with visible light is impossible owing to a substantial overlap of the absorption spectra of both isomers. details HAA3710 H-L-Phe(4-N=NPh)-OH*HCl
Photoswitches are a subtype of molecular switch that undergo a reversible structural change upon irradiation with light to adopt a different configuration. Activation of a molecular switch by light offers several advantages. In addition to being traceless, light can be precisely controlled in its intensity (dosage control) and can be focused with sub-micron accuracy with a high temporal and spatial reso lution. Consequently, photoswitches ideally lend themselves to the construction of light-responsive pharmaceutical compounds, a field that is described by the term photopharmacology.
Product
H N N N O 1.7 nm 1.0 nm VisUVor Δ Fig.
N
4-Phenylazo-L-phenylalanine hydrochloride OH (S) O H2N NN CAS-No. 2137036-84-9 Formula C15H15N3 O 2*HCl Mol. weight 269,30*36,45 g/mol
→ In Vivo Photopharmacology; K. Hull, J. Morstein, D. Trauner; Chem Rev 2018; 118: 10710-10747. https://doi.org/10.1021/acs.chemrev.8b00037
Photoswitchable peptides for spatiotemporal control of biological functions; L. Albert, O. Vazquez; Chem Commun (Camb) 2019; 55: 10192-10213. https://doi.org/10.1039/c9cc03346g
Product details Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation 24 HAA3910 H-L-Phe(4-N=NPhCH2Cl)-OH*HCl hydrochloride4-{[3-(Chloromethyl)phenyl]azo}-L-phenylalanine OH (S) O H2N NN Cl CAS-No. 1597466-70-0 net Formula C16 H16 ClN3 O 2*HCl Mol. weight 317,77*36,45 g/mol BAA1660 Boc-L-Phe(4-N=NPh)-OH lanineN-alpha-t-Butyloxycarbonyl-4-phenylazo-L-phenyla OH (S) O NHO O NN CAS-No. 134816-33-4 Formula C 20 H23 N3 O4 Mol. weight 369,41 g/mol FAA7010 Fmoc-L-Phe(4-N=NPh)-OH zo-L-phenylalanineN-alpha-(9-Fluorenylmethyloxycarbonyl)-4-phenyla OH (S) O NHO O NN CAS-No. 210366-26-0 Formula C 30 H25N3 O4 Mol. weight 491,54 g/mol References: → Photochemical Control of Drug Efficacy: A Comparison of Uncaging and Photoswitching Ifenprodil on NMDA Receptors; E. R. Thapaliya, L. Mony, R. Sanchez, B. Serraz, P. Paoletti, G. C. R. Ellis‐Davies; ChemPhotoChem 2021; 5: 445-454. https://doi.org/10.1002/cptc.202000240 → Photopharmacology and Photochemical Biology; A. Deiters, S. Kossatz, O. Vázquez; ChemPhotoChem 2021; 5: 1031-1032. https://doi.org/10.1002/cptc.202100216 → Short Photoswitchable Antibacterial Peptides; Y. Q. Yeoh, J. R. Horsley, J. Yu, S. W. Polyak, B. Jovcevski, A. D. Abell; ChemMedChem 2020; 15: 1505-1508. https://doi.org/10.1002/cmdc.202000280 → Chapter Eleven - Photopharmacological control of lipid function; J. Morstein, D. Trauner; Meth. Enzymol. 2020; 638: 219-232. https://doi.org/10.1016/bs.mie.2020.04.025 → Visible-Light Photoswitching by Azobenzazoles; A. D. W. Kennedy, I. Sandler, J. Andreasson, J. Ho, J. E. Beves; Chemistry 2020; 26: 1103-1110. https://doi.org/10.1002/chem.201904309 → Light Regulation of Enzyme Allostery through Photo-responsive Unnatural Amino Acids; A. C. Kneuttinger, K. Straub, P. Bittner, N. A. Simeth, A. Bruckmann, F. Busch, C. Rajendran, E. Hupfeld, V. H. Wysocki, D. Horinek, B. Konig, R. Merkl, R. Sterner; Cell Chem Biol 2019; 26: 1501-1514 e9. https://doi.org/10.1016/j.chembiol.2019.08.006 → Genetically encoding photoswitchable click amino acids for general optical control of conformation and function of proteins; C. Hoppmann, L. Wang; Meth. Enzymol. 2019; 624: 249-264. https://doi.org/10.1016/bs.mie.2019.04.016 →
→ Photocontrol of Antibacterial Activity: Shifting from UV to Red Light Activation; M. Wegener, M. J. Hansen, A. J. M. Driessen, W. Szymanski, B. L. Feringa; J Am Chem Soc 2017; 139: 17979-17986. https://doi.org/10.1021/jacs.7b09281 back to content arrow-up
Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation Photochemistry 25 → Photopharmacological control of bipolar cells restores visual function in blind mice; L. Laprell, I. Tochitsky, K. Kaur, M. B. Manookin, M. Stein, D. M. Barber, C. Schon, S. Michalakis, M. Biel, R. H. Kramer, M. P. Sumser, D. Trauner, R. N. Van Gelder; J Clin Invest 2017; 127: 2598-2611. https://doi.org/10.1172/JCI92156 → Emerging Targets in Photopharmacology; M. M. Lerch, M. J. Hansen, G. M. van Dam, W. Szymanski, B. L. Feringa; Angew. Chem. Int. Ed. 2016; 55: 10978-99. https://doi.org/10.1002/anie.201601931 → Genetically encoding photoswitchable click amino acids in Escherichia coli and mammalian cells; C. Hoppmann, V. K. Lacey, G. V. Louie, J. Wei, J. P. Noel, L. Wang; Angew. Chem. Int. Ed. 2014; 53: 3932-6. https://doi.org/10.1002/anie.201400001 → Reversible photocontrol of biological systems by the incorporation of molecular photoswitches; W. Szymanski, J. M. Beierle, H. A. Kistemaker, W. A. Velema, B. L. Feringa; Chem Rev 2013; 113: 6114-78. https://doi.org/10.1021/cr300179f → Photoisomerization in different classes of azobenzene; H. M. Bandara, S. C. Burdette; Chem Soc Rev 2012; 41: 1809-25. https://doi.org/10.1039/c1cs15179g → Azobenzene photoswitches for biomolecules; A. A. Beharry, G. A. Woolley; Chem Soc Rev 2011; 40: 4422-37. https://doi.org/10.1039/c1cs15023e → Properties of the pyramidal tract neuron system within the precentral wrist and hand area of primate motor cortex; D. R. Humphrey, W. S. Corrie, R. Rietz; J Physiol (Paris) 1978; 74: 215-26. https://doi.org/10.1016/j.isci.2021.102771 .circle-arrow-right Do you require serviceInquirephotoactivateddifferentcompounds?withourCustomSynthesisandorderourbooklet.
Photocleavable Auxiliary Reagent for Native Chemical Ligation
Native Chemical Ligation is one of the most powerful tools for the preparation of complex peptides and small proteins. However, the classical variant of NCL requires an N-terminal cysteine at the ligation site. Iris Biotech presents an innovative auxiliary reagent for NCL that can be incorporated in place of a glycine residue.
Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation 26 .8.
Since glycine usually occurs several times in a peptide sequence, this approach significantly increases variability regarding the choice of possible ligation sites. In Native Chemical Ligation, the auxiliary’s SH-group mimics the action of an N-terminal cysteine’s sulfhydryl group.
Fig. 11: Native Chemical Ligation utilizing the photocleavable NCL-auxiliary glycine building block (PAA2000). back to content arrow-up
Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation Photochemistry 27 Following SPPS, the auxiliary is attached to the N-terminus of a peptide sequence in lieu of a glycine residue. The auxiliary’s Fmoc-protected amino functionality can subsequently be deprotected and functionalized, e.g. with a monodisperse PEG. PEGylation is useful for increasing the solubility of peptide fragments, and for facilitating their purification by precipitation with EtOH/Et 2O. These properties are especially valuable if the peptide’s amino acid side chains are supposed to be further derivatized postSPPS, for example by enzymatic glycosylation. Following NCL, the auxiliary can be conveniently removed by irradiation with UV-light (10 min in water or water/acetonitrile). This method is particularly useful for the synthesis of sophisticated peptides such as glycopeptides, where cost- and labor-intensive short sequences can be prepared separately, and subsequently conjugated to long fragments synthesized in a standard manner. Product details PAA2000 tBu-SS-Photo(Fmoc)-Gly-OH Photocleavable-NCL-auxiliary-Gly-OH OH NH S S O NO2 MeO O HN O NH O O Formula C 36 H44N4O 9 S 2 Mol. weight 740,89 g/mol Reference: → A PEGylated photocleavable auxiliary mediates the sequential enzymatic glycosylation and native chemical ligation of peptides; C. Bello, S. Wang, L. Meng, K. W. Moremen, C. F. Becker; Angew. Chem. Int. Ed. 2015; 54: 7711-5. https://doi.org/10.1002/anie.201501517 .circle-arrow-right For more information on Ligation downloadTechnologies,ourbrochure!
Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation 28 .9. Photo-Linker for Solid Phase Synthesis of Peptide Amides and Acids Peptide linkers are usually cleaved under acidic conditions or using two-step procedures. Photocleavage proceeds under neutral conditions using UV light and can either be performed in batch or using flow chemistry. ResinP T I ED LinkerEP P T I EDEP hν Fig. 12: Cleavage of photolabile linkers. Furthermore, photolabile linkers are orthogonal to standard peptide chemistry reaction conditions, thus enabling the use of a wide variety of amino acid protecting groups. Three different photolabile linkers are available for your convenience: Photo-linker for the synthesis of C-terminal carboxylic acids Product details RL-2150 Acid-Photo-Linker butanoic4-(4-(1-hydroxyethyl)-2-methoxy-5-nitrophenoxy)acid O2N OMe HO O OOHCAS-No. 175281-76-2 Formula C13 H17NO 7 Mol. weight 299,28 g/mol back to content arrow-up
Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation Photochemistry 29 Fmoc-amino photo-linker for the synthesis of peptide amides Product details RL-1026 Fmoc-Photo-Linker methoxy-5-nitrophenoxy}butanoic4-{4-[1-(9-Fluorenylmethyloxycarbonylamino)ethyl]-2-acid O O2N OHO OMe NHOOCAS-No. 162827-98-7 Formula C 28 H28 N2O 8 Mol. weight 520,56 g/mol BR-5205 Fmoc-Photolabile Resin oxy}butanamide4-{4-[1-(Fmoc-amino)-ethyl]-2-methoxy-5-nitrophenpolystyrene O Me NO2 Me ONH O HN O References: → Continuous photochemical cleavage of linkers for solid-phase synthesis; M. Hurevich, J. Kandasamy, B. M. Ponnappa, M. Collot, D. Kopetzki, D. T. McQuade, P. H. Seeberger; Org Lett 2014; 16: 1794-7. https://doi.org/10.1021/ol500530q → Photolytic Mass Laddering for Fast Characterization of Oligomers on Single Resin Beads; K. Burgess, C. I. Martinez, D. H. Russell, H. Shin, A. J. Zhang; J. Org. Chem. 1997; 62: 5662-5663. https://doi.org/10.1021/jo970866w → Direct Monitoring of Organic Reactions on Polymeric Supports; M. R. Carrasco, M. C. Fitzgerald, Y. Oda, S. B. H. Kent; Tetrahedron Lett. 1997; 38: 6331-6334. https://doi.org/10.1016/s0040-4039(97)01456-1 .circle-arrow-right Download our Resin Guideline and explore the complete range of resins available at Iris Biotech!
The unnatural amino acid Aca (7-amino-coumarin-4-acetic acid) is a coumarin derivative and thus exhibits fluorescence. When incorporated into a peptide C-terminally of phenylalanine, Aca is a useful reporter group for the successful internalization of CPPs. The phenyl moiety of Phe quenches the fluorescence of Aca. Internalization of the CPP containing Phe-Aca leads to proteolytic cleavage of the Phe-Aca bond and thus to fluorescence. However, the peptide bond formation between Phe and Aca is considered to be a difficult coupling and often leads to low coupling yields. For your convenience, Iris Biotech offers Fmoc Phe-Aca as building block suitable for SPPS. This pseudodipeptide can be coupled to the resin of your choice and subsequently elongated to prepare your target cell penetrating peptides.
Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation 30 .10. Related Products 10.1. Fmoc-Phe-Aca- a Cell Internalization Reporter, and further Fluorescent Amino Acid Derivatives
N H O H ON O O O OH O N H O H ON O O O X O Solid Support LoadingSPPS N H O H N O O OH O HCPP 2N Quenching Cell Internalization and CleavageProteolytic H2N O O OH O X = O or N Fig. 13: Loading of a solid support, subsequent elongation to CPPs and function as a reporter group for successful CPP internalization. back to content arrow-up
The Fmoc-L-Phe-Aca pseudo-dipeptide is a useful reporter group for the successful internalization of CPPs. Phe quenches the fluorescence of Aca. Internalization of the peptide containing Phe-Aca leads to proteolytic cleavage of the Phe-Aca bond and thus to fluorescence.
In addition to Fmoc-L-Phe-Aca-OH, we offer various 7-amino-4-methylcoumarin (AMC)-functionalized amino acid derivatives. Like Aca, when bound to a peptide, the AMC-amide fluoresces very weakly and excitation/emission wavelengths are shorter (ca. 330/390 nm). When the free AMC-amine is released by proteolytic cleavage, the fluorescence increases by a factor of approx. 700 and excitation and emission wavelengths are red-shifted. Thus, the low fluorescence of the AMC-amide substrate does not interfere with the fluorometric assay. Besides, Iris Biotech offers dipeptide recognition motifs such as Phe-Arg (ZAA1480) or Arg-Arg (ZAA1470) as fluorogenic 7-amido-4-methylcoumarin based protease substrates.
The acetic acid derivative of AMC, 7-amino-4-methyl coumarin-3-acetic acid (AMCA) emits in the blue region (440-460 nm) upon activation with UV light of 350 nm. fluorescent amino acids include those functionalized with acridine derivatives (2-Acd and 2-Bacd).
Further
Coumarin Derivatives Product details BAA3650 Boc-L-Lys-AMC*AcOH N-alpha-t-Butyloxycarbonyl-L-lysine 7-ami do-4-methylcoumarin acetate HN (S) O NH NH2 O O O OCAS-No. 116883-12-6 net Formula C 21H29 N3 O 5*CH3 CO 2H Mol. weight 403,47*60,05 FDP1240 Fmoc-L-Phe-Aca-OH laninyl-amido]-coumarin-4-acetic7-[N-alpha-(9-Fluorenylmethyloxycarbonyl)-L-phenylaacid HN(S) O NHO O O OHO O CAS-No. 2250437-40-0 Formula C 35H28 N2O 7 Mol. weight 588,61 g/mol HAA1200 H-L-Ala-AMC L-Alanine-7-amido-4-methylcoumarin O ONH O H2NCAS-No. 77471-41-1 Formula C13 H14N2O 3 Mol. weight 246,27 g/mol HAA7760 H-L-Thr-AMC L-Threonine 7-amido-4-methylcoumarin, 98% (S) O H2N HN O O HO CAS-No. 191723-66-7 Formula C14H16 N2O4 Mol. weight 276,29 g/mol
Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation Photochemistry 31
Product details Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation 32 HAA1174 H-L-Ala-AMC*TFA L-Alanine 7-amido-4-methylcoumarin trifluoroacetate O H2N HN OO CAS-No. 96594-10-4 Formula C13 H14N2O 3*CF 3 CO 2H Mol. weight 360,29 g/mol HAA7630 H-L-Arg-AMC*2HCl L-Arginine 7-amido-4-methylcoumarin dihydrochloride (S) H2N HN O O O HN NH NH2 CAS-No. 113712-08-6 Formula C16 H21N 5 O 3*2HCl Mol. weight 331,37*72,90 g/mol HAA7645 Glt-Gly-Arg-AMC.HCl Glutaryl-glycyl-L-arginine 7-amido-4-methylcoumarin hydrochloride O (Z) ONH O (S)HN O NH NH NH2 NH HCl O HO O CAS-No. 103213-40-7 Formula C 23 H30 ClN 6 O 7 *HCl Mol. weight 502,53*36,46 g/mol HAA3200 H-L-Leu-AMC L-Leucine-7-amido-4-methylcoumarine (S) O H2N HN O O CAS-No. 66447-31-2 Formula C16 H20 N2O 3 Mol. weight 288,34 g/mol HAA7740 H-L-Pyr-AMC L-Pyroglutamic acid 7-amido-4-methylcoumarin (S) O HN O ONH O CAS-No. 66642-36-2 Formula C15H14N2O4 Mol. weight 286,29 g/mol HAA2890 H-L-Asp(AMC)-OH L-Aspartic acid beta-(7-amido-4-methylcoumarin) OH(S) O H2N HN O O O CAS-No. 133628-73-6 Formula C14H14N2O 5 Mol. weight 290,27 g/mol back to content arrow-up
Photochemistry Product details Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation33 HAA7971 H-Gly-AMC Glycine 7-amido-4-methylcoumarin H2N HN O O O CAS-No. 77471-42-2 Formula C12H12N2O 3 Mol. weight 232,24 g/mol RL-1005 AMCA-OSu 7-Amino-4-methyl-3-coumarinylacetyl succinimidyl ester AMCO-NHS O O O OH2N N O O CAS-No. 113721-87-2 Formula C16 H14N2O 6 Mol. weight 330,29 g/mol RL-1170 Fmoc-ACA-OH rin-4-acetic7-(9-Fluorenylmethyloxycarbonylamino)-coumaacid O OHN OH O O OCAS-No. 378247-75-7 Formula C 26 H19 NO 6 Mol. weight 441,43 g/mol ZAA1470 Z-L-Arg-L-Arg-AMC*2HCl do-4-methylcoumarin-dihydrochlorideN-alpha-benzyloxycarbonyl-L-arginyl-L-arginine-7-ami O NH O HN O NH O O O NH NHNH2 NHNH2HN CAS-No. 88937-61-5 (net) Formula C 30 H39 N9 O 6*2HCl Mol. weight 621,69*72,91 g/mol ZAA1480 Z-L-Phe-L-Arg-AMC*HCl ne-7-amido-4-methylcoumarinN-alpha-benzyloxycarbonyl-L-phenylalanyl-L-arginihydrochlorid O NH O HN O NH O O O NH NHNH2 CAS-No. 65147-22-0 Formula C 33 H36 N 6 O 6*HCl Mol. weight 612,69*36,46 g/mol
Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation 34 Acridine Derivatives Product details BAA1570 Boc-L-Ala(2-Bacd)-OCH2CN on-2-yl]-L-alanineN-alpha-t-Butyloxycarbonyl-3-[benzo[b]acridin-12(5H)-cyanomethylester NH (S) O O O O OHN N CAS-No. 1213074-87-3 Formula C 27H25N3 O 5 Mol. weight 471,5 g/mol BAA1580 Boc-L-Ala(2-Bacd)-OH on-2-yl]-L-alanineN-alpha-t-Butyloxycarbonyl-3-[benzo[b]acridin-12(5H)- NH (S) OH O O O OHNCAS-No. 916834-72-5 Formula C 25H24N2O 5 Mol. weight 432,47 g/mol BAA1590 Boc-L-Ala(2-Acd)-OH nyl]}-L-alanineN-alpha-t-Butyloxycarbonyl-3-{2-[9(10H)-acrido NH (S) OH O O O OHNCAS-No. 643018-86-4 Formula C 21H22N2O 5 Mol. weight 382,41 g/mol FAA5830 Fmoc-L-Ala(2-Acd)-OH nyl)-3-{2-[9(10H)-acridonyl]}-L-alanineN-alpha-(9-Fluorenylmethoxycarbo NH (S) OH O O O OHNCAS-No. 1013328-63-6 Formula C 31H24N2O 5 Mol. weight 504,53 g/mol FAA5880 Fmoc-L-Ala(2-Bacd)-OH acridin-12(5H)-on-2-yl]-L-alanineN-alpha-(9-Fluorenylmethoxycarbonyl)-3-[benzo[b] NH (S) OH O O O OHNCAS-No. 1157859-85-2 Formula C 35H26 N2O 5 Mol. weight 554,59 g/mol back to content arrow-up
→ Determination of Caspase Specificities Using a Peptide Combinatorial Library; N. A. Thornberry, K. T. Chapman, D. W. Nicholson; Method Enzymol 2000; 322: 100-110. https://doi.org/10.1016/S0076-6879(00)22011-9
→ Sensitive assays for trypsin, elastase, and chymotrypsin using new fluorogenic substrates; M. Zimmerman, B. Ashe, E. C. Yurewicz, G. Patel; Anal. Biochem. 1977; 78(1): 47-51. https://doi.org/10.1016/0003-2697(77)90006-9.
→ Synthesis of a New Fluorogenic Substrate for Cystine Aminopeptidase; Y. Kanaoka, T. Takahashi, H. Nakayama, T. Ueno, T. Sekine; Chem. Pharm. Bull. 1982; 30(40) : 1485-1487. https://doi.org/10.1248/cpb.30.1485.
→ A Simple Fluorescent Labeling Method for Studies of Protein Oxidation, Protein Modification, and Proteolysis; A. M. Pickering, K. J. A. Davies; Free Radic Biol Med. 2012; 52(2) : 239-246. https://doi.org/10.1016/j.freeradbiomed.2011.08.018.
→ Fluorescence imaging of drug target proteins using chemical probes; H. Zhu, I. Hamachi; J. Pharm. Anal. 2020; 10: 426-433. https://doi.org/10.1016/j.jpha.2020.05.013.
→ A New Fluorogenic Substrate for Chymotrypsin; M. Zimmerman, E. Yurewicz, G. Patel; Anal. Biochem. 1976; 70: 258-262. https://doi.org/10.1016/S0003-2697(76)80066-8.
→ Aminomethyl coumarin acetic acid: a new fluorescent labelling agent for proteins; H. Khalfan, R. Abuknesha, M. Rand-Weaver, R. G. Price, D. Robinson; Histochem J. 1986; 18(9) : 497-499. https://doi.org/10.1007/BF01675617.
Photochemistry Product details Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation35 HAA3570 H-L-Ala(2-Bacd)-OH*HCl 3-[Benzo[b]acridin-12(5H)-on-2-yl]-L-alanine hydroch loride H2N (S) OH O OHNFormula C 20 H16 N2O 3*HCl Mol. weight 332,35*36,45 g/mol HAA3580 H-L-Ala(2-Acd)-OH*HCl 3-{2-[9(10H)-acridonyl]}-L-alanine hydrochloride H2N (S) OH O OHNCAS-No. 854503-32-5 net Formula C16 H14N2O 3*HCl Mol. weight 282,29*36,45 g/mol References: → Rapid and general profiling of protease specificity by using combinatorial fluorogenic substrate libraries; J. L. Harris, B. J. Backes, F. Leonetti, S. Mahrus, J. A. Ellman, C. S. Craik; PNAS 2000; 97: 7754-7759. https://doi.org/10.1073/pnas.140132697 → Expedient Solid-Phase Synthesis of Fluorogenic Protease Substrates Using the 7-Amino-4-carbamoyl methylcoumarin (ACC) Fluorophore; D. J. Maly, F. Leonetti, B. J. Backes, D. S. Dauber, J. L. Harris, C. S. Craik, J. A. Ellman; J. Org. Chem. 2002; 67: 910-915. https://doi.org/10.1021/jo016140o
Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation 36 10.2. Building Blocks for the SPPS of FRET-based fluorogenic protease substrates The classic FRET pair EDANS and DABCYL is now available linked to Fmoc amino acid building blocks that can be readily used in SPPS. Conveniently synthesize your own custom protease substrates! Peptide Fragment 1 EDANS DABCYL FRET EDANS 340 nm FragmentDABCYL2 Proteolysis 490 nm 340 nm Fig. 14: Screening of protease activity using FRET-based fluorogenic protease substrates Traditionally, fluorogenic protease substrates for the screening of protease activity are prepared by peptide synthesis and subsequent regioselective deprotection and functionalization with a fluorophore/ quencher pair such as EDANS and DABSYL. For your convenience, we now offer a glutamate and a lysine building block functionalized with EDANS and DABSYL, respectively. Those building blocks are suitable for peptide synthesis using the Fmoc strategy and will allow you to prepare custom protease substrates without additional tedious and yield-reducing functionalization steps post-SPPS. Product details FAA1498 Fmoc-L-Lys(Dabcyl)-OH lon-4-[4‘-(dimethylamino)phenylazo]benzoyl-L-lysineN-alpha-(9-Fluorenylmethyloxycarbonyl)-N-epsi (S) O NH HN O O O OH NN N Me Me CAS-No. 146998-27-8 Formula C 36 H37N 5 O 5 Mol. weight 619,73 g/mol FAA4410 Fmoc-L-Glu(EDANS)-OH naphthalen-1-ylamino)ethylamido)-L-glutamicN-alpha-(9-Fluorenylmethyloxycarbonyl)-5-(2-(5-sulfoacid OH(S) O HN NHO OO NH S O O OH CAS-No. 193475-66-0 Formula C 32H31N3 O 8 S Mol. weight 617,67 g/mol back to content arrow-up
https://doi.org/10.1021/jm00099a001 →
Photochemistry Product details Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation37 LS-4180 Dabcyl-KTSAVLQSGFRKM-Glu(Edans)-amide nyl-glutamyl(Edans)-amideminyl-seryl-glycyl-phenylalanyl-arginyl-lysyl-methioDabcyl-lysyl-threonyl-seryl-alanyl-valyl-leucyl-gluta H CHHO H H N O H H HN C O NH N N OH HN Formula C95H142N26 O 23 S 2 Mol. weight 2080,46 g/mol References: → Enzymatic activity characterization of SARS coronavirus 3C-like protease by fluorescence resonance energy transfer technique; S. Chen, L. L. Chen, H. B. Luo, T. Sun, J. Chen, F. Ye, J. H. Cai, J. K. Shen, X. Shen, H. L. Jiang; Acta Pharmacol Sin 2005; 26: 99-106. https://doi.org/10.1111/j.1745-7254.2005.00010.x → Synthesis and evaluation of fluorescent probes for the detection of calpain activity; S. Mittoo, L. E. Sundstrom, M. Bradley; Anal Biochem 2003; 319: 234-8. https://doi.org/10.1016/s0003-2697(03)00324-5
→ A general method for the preparation of internally quenched fluorogenic protease substrates using solid-phase peptide synthesis; L. L. Maggiora, C. W. Smith, Z. Y. Zhang; J Med Chem 1992; 35: 3727-30. Novel fluorogenic substrates for assaying retroviral proteases by resonance energy transfer; E. D. Matayoshi, G. T. Wang, G. A. Krafft, J. Erickson; Science 1990; 247: 954-8. https://doi.org/10.1126/science.2106161
→ Design and synthesis of new fluorogenic HIV protease substrates based on resonance energy transfer; G. T. Wang, E. Matayoshi, H. Jan Huffaker, G. A. Krafft; Tetrahedron Lett. 1990; 31: 6493-6496. https://doi.org/10.1016/s0040-4039(00)97099-0
Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation 38 Notes back to content arrow-up
As business activity of Iris Biotech GmbH impacts people’s lives and health, it must be operated in et hical and correct manner and act with integrity and responsibility. To ensure high ethical standards and fair business practices, Iris Biotech GmbH applies an integrated policy known as its Code of Conduct. In 2001 Iris Biotech GmbH was founded just at the beginning of the Biotech movement and the first remarkable breakthrough of biotech pharma products. Although the biotech field is rather young com pared to other industries we believe on long-term business, a good partnership between our business partners and Iris Biotech GmbH and a good reputation. It is our duty as well as our responsibility to maintain and to extend this over the next generations – based on the principles of an honourable and prudent tradesman which based upon the concept of honourable entrepreneurship.
39 Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation PhotochemistryCodeof
Conduct
This Code of Conduct has been developed following the “Voluntary Guidelines for Manufacturers of Fine Chemical Intermediates and Active Ingredients” issued by AIME (Agrochemical & Intermediates Manufac turers in Europe) and the requirements of some of our business associates.
Iris Biotech GmbH commits to hold this Code of Conduct and to include and apply its principles in the management system and the company policies. Ethics Iris Biotech GmbH undertakes business in an ethical manner and acts with integrity. All corruption, ex tortion and embezzlement are prohibited. We do not pay or accept bribes or participate in other illegal inducements in business or government relationships. We conduct our business in compliance with all applicable anti-trust laws. Employees are encouraged to report concerns or illegal activities in the work place, without threat of reprisal, intimidation or harassment. Labour Iris Biotech GmbH is committed to uphold the human rights of workers and to treat them with dignity and respect. Child labour, workplace harassment, discrimination, and harsh and inhumane treatment are prohibited. Iris Biotech GmbH respects the rights of the employees to associate freely, join or not join labour unions, seek representation and join workers’ councils. Employees are paid and their working timetable is established according to applicable wage and labour laws. Employees are able to commu nicate openly with management regarding working conditions without threat of reprisal, intimidation or harassment.
General Policies Contracts and Secrecy Agreements are binding and the confidential information received is only used for intended purposes. Clear management and organizational structures exist to provide efficient normal working and to address problems quickly. Know-how is protected and intellectual property isrespected.
Health and Safety Iris Biotech GmbH provides a safe and healthy working environment to the employees and protects them from overexposure to chemical and physical hazards. Products are produced, stored and shipped under the guidelines of the relevant chemical and safety legislation. Risks and emergency scenarios are identified and evaluated, and their possible impact is minimized by implementing emergency plans and written procedures. Safety information regarding hazardous materials is available to educate, train and protect workers from hazards. Preventive equipment and facilities maintenance is performed at suitable periods to reduce potential hazards. Employees are regularly trained in health and safety matters and are informed about product properties and risk classification when it is required.
A quality management system following the Good Distribution Practices (GDP rules) of Active Pharma ceutical Ingredients is established covering all the aspects of the worldwide distribution of products. Regular audits are performed to evaluate the efficiency and fulfilling of the quality system. Process controls to provide reproducible product quality are established. There are preventive maintenance pro cedures to ensure plant reliability and the lowest risk of failure. Staff is trained periodically about GMP and GDP rules. Procedures are established and installations are designed to avoid cross contamination. Batch and analytical records are kept for inspection and audit purposes for suitable periods according guidelines. Research and Development Research and development staff education is appropriate to their functional activity and they are trained to develop, optimize and scale-up the processes. Intellectual property is respected and knowhow protected. Development of manufacturing processes reflects the principles of the Green Chemistry according to the American Chemical Society Green Chemistry Institute. Animal testing is not used unless alternatives are not scientifically valid or accepted by regulators. If animal testing is carried out, animals are treated so that pain and stress are minimized.
Environment Iris Biotech GmbH operates in an environmentally responsible and efficient manner, minimizing adverse impacts on the environment. Waste streams are managed to ensure a safe handling, movement, storage, recycling and reuse, before and after being generated. Systems to prevent and mitigate accidental spills and releases to the environment are in place. All required environmental permits and licenses are obtai ned and their operational and reporting requirements are complied with.
Production and Quality Management
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40Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation
Every order made by the buyer shall be deemed an offer by the buyer to purchase products from Iris Biotech GmbH and will not be binding on Iris Biotech GmbH until a duly authorised representative of Iris Biotech GmbH has accepted the offer made by the buyer. Iris Biotech GmbH may accept orders from commercial, educational or government organisations, but not from private individuals and Iris Biotech GmbH reserves the right to insist on a written order and/or references from the buyer before procee Thereding. is no minimum order value. At the time of acceptance of an order Iris Biotech GmbH will either ar range prompt despatch from stock or the manufacture/acquisition of material to satisfy the order. In the event of the latter Iris Biotech GmbH will indicate an estimated delivery date. In addition to all its other rights Iris Biotech GmbH reserves the right to refuse the subsequent cancellation of the order if Iris Bio tech GmbH expects to deliver theproduct on or prior to the estimated delivery date. Time shall not be of the essence in respect of delivery of the products. If Iris Biotech GmbH is unable to deliver any products by reason of any circumstances beyond its reasonable control („Force Majeure“) then the period for delivery shall be extended by the time lost due to such Force Majeure. Details of Force Majeure will be forwarded by Iris Biotech GmbH to the buyer as soon as reasonably practicable.
All orders placed by a buyer are accepted and all contracts are made subject to the terms which shall prevail and be effective notwithstanding any variations or additions contained in any order or other do cument submitted by the buyer. No modification of these terms shall be binding upon Iris Biotech GmbH unless made in writing by an authorised representative of Iris Biotech GmbH.
PhotochemistryTermsand Conditions of Sales
Placing of Orders
41 Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation
Prices, Quotations and Payments Prices are subject to change. For the avoidance of doubt, the price advised by Iris Biotech GmbH at the time of the buyer placing the order shall supersede any previous price indications. The buyer must contact the local office of Iris Biotech GmbH before ordering if further information is required. Unless otherwise agreed by the buyer and Iris Biotech GmbH, the price shall be for delivery ex-works. In the event that the buyer requires delivery of the products otherwise than ex-works the buyer should contact the local office of Iris Biotech GmbH in order to detail its requirements. Iris Biotech GmbH shall, at its discretion, arrange the buyer‘s delivery requirements including, without limitation, transit insurance, the mode of transit (Iris Biotech GmbH reserves the right to vary the mode of transit if any regulations or other relevant considerations so require) and any special packaging requirements (including cylinders). For the avoidance of doubt all costs of delivery and packaging in accordance with the buyer‘s requests over and above that of delivery in standard packaging ex-works shall be for the buyer‘s account un less otherwise agreed by both parties. Incoterms 2020 shall apply. Any tax, duty or charge imposed by governmental authority or otherwise and any other applicable taxes, duties or charges shall be for the buyer‘s account. Iris Biotech GmbH may, on request and where possible, provide quotations for multiple packs or bulk quantities, and non-listed items. Irrespective of the type of request or means of response all quotations must be accepted by the buyer without condition and in writing before an order will be accepted by Iris Biotech GmbH. Unless agreed in writing on different terms, quotations are valid for 30 days from the date thereof. Payment terms are net 30 days from invoice date unless otherwise agreed in writing. Iris Biotech GmbH reserves the right to request advance payment at its discretion. For over seas transactions the buyer shall pay all the banking charges of Iris Biotech GmbH. The buyer shall not be entitled to withhold or set-off payment for the products for any reason whatsoever. Government/
Corporate Visa and MasterCard (and other such credit cards) may be accepted on approved accounts for payment of the products. Personal credit cards are not acceptable. Failure to comply with the terms of payment of Iris Biotech GmbH shall constitute default without reminder. In these circumstances Iris Bio tech GmbH may (without prejudice to any other of its rights under these terms) charge interest to accrue on a daily basis at the rate of 2% per month from the date upon which payment falls due to the actual date of payment (such interest shall be paid monthly). If the buyer shall fail to fulfil the payment terms in respect of any invoice of Iris Biotech GmbH Iris Biotech GmbH may demand payment of all outstan ding balances from the buyer whether due or not and/or cancel all outstanding orders and/or decline to make further deliveries or provision of services except upon receipt of cash or satisfactory securities.
Technical information, provided orally, in writing, or by electronic means by or on behalf of Iris Biotech GmbH, including any descriptions, references, illustrations or diagrams in any catalogue or brochure, is provided for guidance purposes only and is subject to change. Safety All chemicals should be handled only by competent, suitably trained persons, familiar with laboratory procedures and potential chemical hazards. The burden of safe use of the products of Iris Biotech GmbH vests in the buyer. The buyer assumes all responsibility for warning his employees, and any persons who might reasonably be expected to come into contact with the products, of all risks to person and pro perty in any way connected with the products and for instructing them in their safe handling and use.
The buyer shall inspect goods immediately on receipt and inform Iris Biotech GmbH of any shortage or damage within five days. Quality problems must be notified within ten days of receipt. Goods must not be returned without prior written authorisation of Iris Biotech GmbH. Iris Biotech GmbH shall at its sole discretion replace the defective products (or parts thereof) free of charge or refund the price (or pro portionate price) to buyer. Opened or damaged containers cannot be returned by the buyer without the written prior agreement of Iris Biotech GmbH. In the case of agreed damaged containers which cannot be so returned, the buyer assumes responsibility for the safe disposal of such containers in accordance with all applicable laws.
Product Quality, Specifications and Technical Information Products are analysed in the Quality Control laboratories of Iris Biotech GmbH’s production partners by methods and procedures which Iris Biotech GmbH considers appropriate. In the event of any dispute concerning reported discrepancies arising from the buyer’s analytical results, determined by the buyer’s own analytical procedures, Iris Biotech GmbH reserves the right to rely on the results of own analytical methods of Iris Biotech GmbH. Certificates of Analysis or Certificates of Conformity are available at the discretion of Iris Biotech GmbH for bulk orders but not normally for prepack orders. Iris Biotech GmbH reserves the right to make a charge for such certification. Specifications may change and reasonable variation from any value listed should not form the basis of a dispute. Any supply by Iris Biotech GmbH of bespoke or custom product for a buyer shall be to a specification agreed by both parties in writing.
The buyer also assumes the responsibility for the safe disposal of all products in accordance with all applicable laws. back to content arrow-up
42Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation
Shipping, Packaging and Returns
Until payment by the buyer in full of the price and any other monies due to Iris Biotech GmbH in respect of all other products or services supplied or agreed to be supplied by Iris Biotech GmbH to the buyer (including but without limitation any costs of delivery) the property in the products shall remain vested in Iris Biotech GmbH.
All products of Iris Biotech GmbH are intended for laboratory research purposes and unless otherwi se stated on product labels, in the catalogue and product information sheet of Iris Biotech GmbH or in other literature furnished to the buyer, are not to be used for any other purposes, including but not limited to use as or as components in drugs for human or animal use, medical devices, cosmetics, food additives, household chemicals, agricultural or horticultural products or pesticides. Iris Biotech GmbH offers no warranty regarding the fitness of any product for a particular purpose and shall not be respon sible for any loss or damage whatsoever arising there from. No warranty or representation is given by Iris Biotech GmbH that the products do not infringe any letters patent, trademarks, registered designs or other industrial rights. The buyer further warrants to Iris Biotech GmbH that any use of the products in the United States of America shall not result in the products becoming adulterated or misbranded within the meaning of the Federal Food, Drug and Cosmetic Act (or such equivalent legislation in force in the buyer‘s jurisdiction) and shall not be materials which may not, under sections 404, 505 or 512 of the Act, be introduced into interstate commerce.
43 Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation PhotochemistryUses,Warranties and Liabilities
The buyer acknowledges that, since the products of Iris Biotech GmbH are intended for research purposes, they may not be on the Toxic Substances Control Act 1976 („TSCA“) inventory. The buyer warrants that it shall ensure that the products are approved for use under the TSCA (or such other equivalent legislation in force in the buyer‘s jurisdiction), if applicable. The buyer shall be responsible for complying with any legislation or regulations governing the use of the products and their importation into the country of destination (for the avoidance of doubt to include, without limitation, the TSCA and all its amendments, all EINECS, ELINCS and NONS regulations). If any licence or consent of any government or other authority shall be required for the acquisition, carriage or use of the products by the buyer the buyer shall obtain the same at its own expense and if necessary produce evidence of the same to Iris Biotech GmbH on demand. Failure to do so shall not entitle the buyer to withhold or delay payment. Any additional expenses or charges incurred by Iris Biotech GmbH resulting from such failure shall be for the buyer‘s account. Save for death or personal injury caused by negligen ce of Iris Biotech GmbH, sole obligation of Iris Biotech GmbH and buyer‘s exclusive remedy with respect to the products proved to the satisfaction of Iris Biotech GmbH to be defective or products incorrectly supplied shall be to accept the return of said products to Iris Biotech GmbH for refund of the actual pur chase price paid by the buyer (or proportionate part thereof), or replacement of the defective product (or part thereof) with alternative product. Iris Biotech GmbH shall have no liability to the buyer under or arising directly or indirectly out of or otherwise in connection with the supply of products by Iris Bio tech GmbH to the buyer and/or their re-sale or use by the buyer or for any product, process or services of the buyer which in any way comprises the product in contract tort (including negligence or breach of statutory duty) or otherwise for pure economic loss, loss of profit, business, reputation, depletion of brand, contracts, revenues or anticipated savings or for any special indirect or consequential damage or loss of any nature except as may otherwise be expressly provided for in these terms. All implied war ranties, terms and representations in respect of the products (whether implied by statute or otherwise) are excluded to the fullest extent permitted by law. The buyer shall indemnify Iris Biotech GmbH for and against any and all losses, damages and expenses, including legal fees and other costs of defending any action, that Iris Biotech GmbH may sustain or incur as a result of any act or omission by the buyer, its of ficers, agents or employees, its successors or assignees, its customers or all other third parties, whether direct or indirect, in connection with the use of any product. For the avoidance of doubt and in the event that Iris Biotech GmbH supplies bespoke or custom product to the buyer‘s design or specification, this indemnity shall extend to include any claim by a third party that the manufacture of the product for the buyer or the use of the product by the buyer infringes the intellectual property rights of any third party.
44Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation General Iris Biotech GmbH shall be entitled to assign or sub-contract all or any of its rights and obligations hereunder. The buyer shall not be entitled to assign, transfer, sub-contract or otherwise delegate any of its rights or obligations hereunder. Any delay or forbearance by Iris Biotech GmbH in exercising any right or remedy under these terms shall not constitute a waiver of such right or remedy. If any provision of these terms is held by any competent authority to be invalid or unenforceable in whole or in part the validity of the other provisions of these terms and the remainder of the provision in question shall not be affected. These terms shall be governed by German Law and the German Courts shall have exclusive jurisdiction for the hearing of any dispute between the parties save in relation to enforcement where the jurisdiction of the German Courts shall be non-exclusive.
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45 Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation PhotochemistryIndex Product code Product name Page RL-2150 Acid-Photo-Linker 28 RL-1005 AMCA-OSu 33 RL-2035 ATFB 12 RL-2045 ATFB-NHS 12 PEG2065 Biotin-TEG-ATFBA 12 BAA1590 Boc-L-Ala(2-Acd)-OH 34 BAA1570 Boc-L-Ala(2-Bacd)-OCH2CN 34 BAA1580 Boc-L-Ala(2-Bacd)-OH 34 BAA3650 Boc-L-Lys-AMC*AcOH 31 BAA1660 Boc-L-Phe(4-N=NPh)-OH 24 BAA3070 Boc-L-Photo-Leucine*DCHA 3 BAA3080 Boc-L-Photo-Lysine 3 BAA3090 Boc-L-Photo-Methionine*DCHA 4 BAA1530 Boc-L-Photo-Phe-OH 4 BAA3100 Boc-L-Photo-Proline 5 LS-4180 Dabcyl-KTSAVLQSGFRKM-Glu(Edans)-amide 37 RL-1170 Fmoc-ACA-OH 33 FAA5660 Fmoc-D-Cys(Npys)-OH 20 FAA5830 Fmoc-L-Ala(2-Acd)-OH 34 FAA5880 Fmoc-L-Ala(2-Bacd)-OH 34 FAA4250 Fmoc-L-Ala(2-Furyl)-OH 18 FAA8420 Fmoc-L-Cys(NDBF)-OH 21 FAA1975 Fmoc-L-Cys(Npys)-OH 20 FAA3970 Fmoc-L-Cys(oNv)-OH 20 FAA4410 Fmoc-L-Glu(EDANS)-OH 36 FAA1498 Fmoc-L-Lys(Dabcyl)-OH 36 FAA8425 Fmoc-L-Lys(NDBFOC)-OH 21 FAA7230 Fmoc-L-Lys(Nvoc)-OH 20 FAA7010 Fmoc-L-Phe(4-N=NPh)-OH 24 FDP1240 Fmoc-L-Phe-Aca-OH 31 FAA4590 Fmoc-L-Photo-Leucine 3 FAA4600 Fmoc-L-Photo-Lysine 3 FAA4610 Fmoc-L-Photo-Methionine 4 FAA5690 Fmoc-L-Photo-Phe-OH 4 FAA4620 Fmoc-L-Photo-Proline 5 FAA7350 Fmoc-N(oNv)-Gly-OH 21 RL-1026 Fmoc-Photo-Linker 29 BR-5205 Fmoc-Photolabile Resin 29 FAA7190 Fmoc-Spr(oNB)-OH 15 Product code Product name Page FAA7200 Fmoc-Spr(oNv)-OH 15, 22 HAA7645 Glt-Gly-Arg-AMC.HCl 32 HAA7971 H-Gly-AMC 33 HAA3580 H-L-Ala(2-Acd)-OH*HCl 35 HAA3570 H-L-Ala(2-Bacd)-OH*HCl 35 HAA2930 H-L-Ala(2-Furyl)-OH 17 HAA1200 H-L-Ala-AMC 31 HAA1174 H-L-Ala-AMC*TFA 32 HAA7630 H-L-Arg-AMC*2HCl 32 HAA2890 H-L-Asp(AMC)-OH 32 HAA9320 H-L-Cys(DMNB)-OH 21 HAA9270 H-L-Cys(MDNPE)-OH 21 HAA3200 H-L-Leu-AMC 32 HAA3710 H-L-Phe(4-N=NPh)-OH*HCl 23 HAA3910 H-L-Phe(4-N=NPhCH2Cl)-OH*HCl 24 HAA3100 H-L-Photo-Leucine*HCl 3 HAA3110 H-L-Photo-Lysine*HCl 3 HAA3120 H-L-Photo-Methionine*HCl 4 HAA3490 H-L-Photo-Phe-OH 4 HAA3130 H-L-Photo-Proline*HCl 5 HAA7740 H-L-Pyr-AMC 32 HAA9255 H-L-Sec(DMNB)-OH*TFA 21 HAA7760 H-L-Thr-AMC 31 PEG5000 N3-TFBA-O2Oc 12 RL-2920 Photo-Benzoic acid 9 RL-2930 Photo-Benzylamine*HCl 10 RL-2910 Photo-Butylamine 10 RL-3410 Photo-Click-Heptanoic acid 9 RL-3720 Photo-Click-Palmitic acid 9 RL-3760 Photo-Click-Stearic acid 9 RL-2900 Photo-Hexanoic acid 8 RL-3740 Photo-Palmitic acid 9 RL-2890 Photo-Pentanoic acid 8 RL-3750 Photo-Stearic acid 9 RL-2970 Photo-Trimethyl-Lock 15, 22 PAA2000 tBu-SS-Photo(Fmoc)-Gly-OH 27 ZAA1470 Z-L-Arg-L-Arg-AMC*2HCl 33 ZAA1480 Z-L-Phe-L-Arg-AMC*HCl 33
46Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation Notes back to content arrow-up
Iris Biotech GmbH • Email: info@iris-biotech.de • www.iris-biotech.de • Empowering Peptide Innovation 48 ChengduChina: Yoo Technology Co., Ltd. Japan: BizCom Japan, Inc. Shigematsu & Co., Ltd Cosmo Bio Co., Ltd. USA & Canada: Peptide Solutions LLC India, Bangladesh, Oman, Sri Lanka, United Arab Emirates: Sumit Biosciences Pvt Ltd. Singapore, Thailand, Malaysia, Indonesia, Vietnam, Philippines, Brunei, Burma (Myanmar), Laos, Cambodia, Timor-Leste: SciClix Pte. Ltd. Iris Biotech GmbH Adalbert-Zoellner-Str. 1 95615 GermanyMarktredwitz +49 (0) 9231 97121-0 +49 (0) 9231 www.iris-biotech.deinfo@iris-biotech.de97121-99 The list contains the current distributors of Iris Biotech in different regions of the world. The latest list of distribution partners and contact details is available at: www.iris-biotech.de/distribution-partner Get in DistributionContactPartners
Empowering Peptide Innovation