Structure of Angiotensin-Converting Enzyme Determined

The structure appeared in an advance online issue of Nature on January 19, 2003.

ACE inhibitors, widely used to treat cardiovascular diseases, have common side effects. ACE consists of two parts, called the N and C domains, with different functions. Current drugs inhibit both domains. The design of specific domain-selective inhibitors is expected to produce next-generation drugs that are safer and more effective, says AngioDesign, Inc. (Lincoln, NE, USA), whose founders determined the ACE structure.

Using the 3D structure, next-generation ACE inhibitors can be created by structure-guided design. According to AngioDesign, this process will involve computational chemistry and molecular modeling, using existing inhibitors as scaffolds, followed by synthesis of new compounds and iterative lead optimization by crystallization. Some of this work will be performed in the laboratories of AngioDesign's founders in Bath, UK, and Cape Town, South Africa. Novel C- and N-domain-selective ACE inhibitors will then be evaluated for further development in partnership with suitable pharmaceutical companies.

AngioDesign focuses on the design of improved, next-generation drugs for proven disease targets. The company's goal is to shorten the process by applying structure-guided drug design.





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