New breakthrough that could lead to safer
drugs for cardiovascular diseases
A scientist from the University of Cape Town (UCT), working in collaboration
with colleagues from the University of Bath (United Kingdom), have developed new
research on the structure of human angiotensin-converting enzyme (ACE) that
could lead to the design of safer and more effective drugs to treat
cardiovascular diseases.
Dr Ed Sturrock of the Department of Clinical Laboratory Sciences and
Medicine at UCT and his collaborator, Professor Ravi Acharya of the
Department of Biology and Biochemistry at the University of Bath, have
determined the three-dimensional crystal structure of angiotensin-converting
enzyme (ACE).
The details of the structure have just been released as an advance online
publication in the journal Nature and
the printed version appears in the January 30 issue of Nature the magazine.
ACE inhibitors are widely used to treat cardiovascular diseases, including
high blood pressure, heart failure, coronary artery disease, as well as
kidney failure. However, use of current-generation ACE inhibitors, which
were developed in the 70s and 80s, has been hampered by common side effects.
Also, ACE actually consists of two parts (called the N and C domains) with
different functions, and current drugs inhibit both domains. Therefore, the
design of specific domain-selective ACE inhibitors is expected to produce
next-generation drugs that are safer and more effective.
Next-generation ACE inhibitors can now be designed by structure-guided drug
design, using the 3-D structure of ACE determined by the founders of
AngioDesign. This process will involve computational chemistry and
molecular modelling, using existing inhibitors as scaffolds, followed by the
synthesis of new compounds and iterative lead optimization by drug-ACE
co-crystallization.
This work will be performed in the laboratories in Bath and at UCT.
Dr Sturrock is a member of the Western Cape Structural Biology Initiative,
which was recently launched at UCT and which will provide an infrastructure for
ongoing research in this field.
"This initiative will ensure that research in this area becomes well
funded
and fruitful, reducing our dependency on first-world countries, says
Sturrock. "The initiative will expedite the development of fully-fledged
research programmes in structural biology," he concluded.
More information:
Contact Dr Sturrock at (021) 650-6312 or 083 752 4950.
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