DRUG DISCOVERY
Fighting neglected and non-communicable diseases Carbonic anhydrases (CAs) catalyze the reaction between water and carbon dioxide to regulate pH and fluid balance in vivo. Deviations in CA activity have been shown to correlate with bone, lung and liver diseases, as well as obesity, type II diabetes and even epilepsy. Professor Areej Abuhammad and her team at the University of Jordan are interested in developing novel therapies to counteract imbalances in CA activity, using protein crystallography to investigate a wide range of potential inhibitors. Carbonic anhydrases are a large group
X-ray crystallography to investigate the
great. And being very simple to set up,
of zinc metallo-enzymes that can
structure of proteins, and how the
and offering versatile applications, it is
reversibly catalyze water and carbon
ligands and inhibitors bind to them.
perfect. Setting up a new lab is always
dioxide – forming hydrogen and
This knowledge is very important for
difficult, especially when working with a
bicarbonate – to alter pH and carbon
structure-based drug discovery,
tight budget, but the Tecan team and
dioxide concentrations. Areej
making it easier to make an informed
local distributor were very supportive,”
Abuhammad, an Associate Professor in
decision on what needs to be altered,
Areej concluded.
Medicinal Chemistry at the University
as well as finding out which functional
of Jordan, is combining her background
groups are responsible for the activity.”
in computer-aided drug design, structural biology and medicinal
“A microplate reader is obviously a key
chemistry to investigate selective
instrument in our research, as we
inhibitors for CA. Areej explained: “The
perform a lot of enzyme activity assays,
function of carbonic anhydrases is to
screening a variety of different
control the pH in the body and, through
inhibitors and enzyme isoforms. I
it, a variety of biological processes.
therefore needed an instrument that
They are therefore linked to the
offers high sensitivity and can handle
etiology of many different pathogenic
small sample sizes, which is essential to
diseases.”
reduce the cost of screening. I also wanted a monochromators-based
“I have always been interested in
system, as we need the flexibility to
neglected diseases; I did my Master’s
perform a wide range of experiments,
degree on avian influenza and, during
screening as many different conditions
my PhD, I worked on drug discovery for
as we want without the limitation of
tuberculosis in the Departments of
filter sets.”
Pharmacology and Biochemistry at the University of Oxford. I moved back to
“After working with a Tecan instrument
Jordan after finishing my PhD, and
during my PhD, I decided to buy an
used the knowledge that I acquired to
Infinite® M Plex reader for our lab in
set up a protein crystallography lab to
Jordan, as this was the best for our lab.
perform research on CAs, combining
It offers the sensitivity and the
drug repurposing with fragment-based
accuracy level we need, while being
drug discovery.”
easy to set up and use. This intuitive operation, together with the system’s
“I am working with isozymes of CAs,
robustness, is something that I really
screening for the new inhibitors and
like about it. We have a lot of Master’s
testing their enzymatic activity. I am
students – as well as offering some
interested in knowing exactly how the
training to undergraduates – and they
inhibitors impact the enzyme; if they
are naïve to the sensitivity of these
inhibit or activate it, and how the
instruments when they first enter the
kinetics work. I also crystallize the
lab. Having a system that can withstand
proteins with the inhibitors and use
this without it compromising results is
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TECAN JOURNAL 2/2021
