Miguel Ondetti
Miguel Angel Ondetti (born May 23, 1930 in Buenos Aires , † August 23, 2004 ) was an Argentine chemist . He and David Cushman developed captopril , the first ACE inhibitor .
Ondetti's parents had Italian ancestors. He attended a business school and worked as an accountant before deciding to study. Since he had not attended a high school, he initially had to study on his own, while he took external exams at the university until he was finally admitted to study chemistry at the University of Buenos Aires. He also worked as an employee. He received his licentiate degree in 1955 and received his doctorate there in 1957 . He conducted research at the Squibb Research Institute in Argentina, mainly looking for new drugs under plant alkaloids , and in 1960 he moved to the Squibb Research Institute in New Jersey, where he worked on peptide chemistry. The strategy was to modify the body's own peptides so that they could be used as drugs, with the focus from 1967 on cardiovascular drugs. Through the Squibb consultant John Robert Vane , he learned about the results of Sérgio Henrique Ferreira about a substance in the jararaca lance viper poison that suppresses the conversion of angiotensin I (via the suppression of the ACE enzyme). They were able to isolate a candidate (Teprotid) but not modify it so that it could be used orally as a drug - the molecule was too large. After randomly screening thousands of substances, Squibb officially abandoned the search in 1973 and Ondetti's group turned to antibiotic research. Secretly, however, they continued their work with a new approach to rational design and made a breakthrough in 1974 with the development of captopril. It entered clinical testing in 1977, received FDA approval in 1981, and was launched in the United States in 1982. The development of captopril was one of the first examples of rational drug design based on the structure of ACE to which the ACE inhibitor was supposed to couple. The structure of ACE itself was not so well known at the time, but it was assumed that it was similar to carboxypeptidase A.
Ondetti became Vice President of Research at Squibb and retired in 1991. In 2007 he was inducted into the National Inventors Hall of Fame . In 1991 he received the Perkin Medal , in 1992 the Warren Alpert Foundation Prize and with David Cushman the ACS Award for Creative Invention and in 1999 with David Cushman the Lasker ~ DeBakey Clinical Medical Research Award . In 1983 he and Cushman and Ferreira received the CIBA Prize for Research on Hypertension. In 1982 he received the GlaxoSmithKline Alfred Burger Award with Cushman.
Fonts
- with EF Sabo: Angiotensin-converting enzyme inhibitors from the venom of Bothrops jararaca. Isolation, elucidation of structure, and synthesis, Biochemistry, Vol. 10, 1971, pp. 4033-4039.
- with B. Rubin, DW Cushman: Design of specific inhibitors of angiotensin-converting enzymes: new class of orally active antihypertensive agents, Science, Volume 196, 1977, pp. 441-444.
Web links
Individual evidence
| personal data | |
|---|---|
| SURNAME | Ondetti, Miguel |
| ALTERNATIVE NAMES | Ondetti, Miguel Angel |
| BRIEF DESCRIPTION | Argentine chemist |
| DATE OF BIRTH | May 23, 1930 |
| PLACE OF BIRTH | Buenos Aires |
| DATE OF DEATH | August 23, 2004 |