Angiotensin-converting enzyme design

Cushman DW, Cheung HS, Sabo EF, Ondetti M A. Design of potent competitive inhibitors of angiotensin-converting enzyme. Carboxyalkanoyl and mercaptoal-kanoyl amino acids. Biochemistry 1977 16 5484-91. 

Redshaw S. Angiotensin-converting enzyme (ACE) inhibitors and the design of captopril. In Ganellin CR, Roberts SM, editors. Medicinal chemistry. The role of organic chemistry in drug research, 2nd edition. Fondon Academic Press, 1993. p. 163-85. 

Yee, S. and G. L. Amidon. Oral absorption of angiotensin-converting enzyme inhibitors and peptide prodrugs. In Peptide-based Drug Design. G. L. Amidon (ed), American Chemistry Society, Washington DC 1995, 137-147. 

D. G. Hangauer, Computer-aided design and evaluation of angiotensin converting enzyme... 

Imatinib mesylate (Gleevec, Novartis), zanamivir (Relenza, GlaxoSmithKline), and oseltamivir (Tamiflu, Roche) are examples of drugs (Exhibits 3.11 and 3.7) that show the successful contributions of rational drug design. For example, the X-ray structure of angiotensin converting enzyme (ACE) has been reported (see Exhibit 11.2), and this may pave the way for more effective ACE inhibitors to be developed for the treatment of hypertension and heart disorders. 

The Design and biological profile of angiotensin-converting enzyme inhibitors, 23, 161 Design of new drugs for helminth diseases Lead optimization in benzimidazoles, 25, 103 Design and therapeutic potential of peptides, 21, 145... 

The 1,2-diazepine Cilazapril 98 is an angiotensin-converting enzyme inhibitor and its design and synthesis have been reported <1986J(P1)1011 1999W099/55724>. 

M. A. Design of Potent Competitive Inhibitors of Angiotensin-Converting Enzyme Carboxyalkanoyl and Mercaptoalkanoyl Amino Acids. Biochemistiy. 1977, 16, 5484-5491. 

One reason for disease is that enzymes may become overactive and it may be necessary to design specific inhibitors for them to treat the disease. Angiotensin-Converting Enzyme (ACE) is a zinc-dependent enzyme that cleaves two amino acids off the end of angiotensin I to give angiotensin II, a protein that causes blood pressure to rise. 

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