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.