Ondetti, Miguel

Ondetti, Miguel Angel (Plate 32) born in 1930 in Buenos Aires, Argentina, completed his studies in chemistry at the University of Buenos Aires in 1957 with a Doctor of Natural Sciences degree received for his work on alkaloid chemistry under V. Deulefeu. Soon after, he joined the Squibb Institute for Medical Research and continued his research at the Institute, also after his transfer to the United States in 1960. There, for several years, he participated in an effort, led by M. Bodanszky, toward the synthesis of peptide hormones, including the first synthesis of secretin and became... 

MA Ondetti, A Miguel, J Krapcho. Mercaptoacyl derivatives of substituted prolines. U.S. Patent 4316906, 1982. 

Dr. David W. Cushman (left) and Dr. Miguel Ondetti (right) developed captopril using a new approach to drug discovery. The captopril team was able to design a molecule with the structure needed to block the active site of the converting angiotensin enzyme (see box 5-A). 

Several peptides isolated from the venom of the South American snake Bothrops jararaca are potent ACE inhibitors and were briefly used for the treatment of hypertension, but were soon superseded by surprisingly simple molecules with high inhibitory effect. At the Squibb Institute for Medical Research in Princeton, New Jersey, Miguel A. Ondetti (Plate 32) recognized that ACE is similar in its substrate specificity to the well studied protease car-boxypeptidase A. He designed, therefore, molecules that should fit into the active site of ACE (presumably similar to the active site of carboxypeptidase A) and form complexes with the enzyme. The dipeptide , 2-D-methyl-3-mercapto-propionyl-L-proline, captopril [7] strongly associated with the enzyme and... 

While Ferreira continued to focus on bradykinin. Sir John R. Vane (1927-2004) and Yeshwant S. Bakhle recognised that the snake venom also had an effect on the renin-angiotensin system. Miguel Ondetti (1930-2004) and David Cushman (1939-2000) at Squibb (now Bristol-Myers-Squibb) isolated and characterised six other ACE-inhibitory peptides, among them teprotide (IC50 250 nM). [7, 8]... 

Miguel A. Ondetti, John T. Sheehan M. Bodanszky The Squibb Institute for Medical Research... 

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