| Autor: |
Cushman DW, Cheung HS, Sabo EF, Ondetti MA |
| Jazyk: |
angličtina |
| Zdroj: |
The American journal of cardiology [Am J Cardiol] 1982 Apr 21; Vol. 49 (6), pp. 1390-4. |
| DOI: |
10.1016/0002-9149(82)90348-4 |
| Abstrakt: |
Captopril is a remarkably effective new antihypertensive drug designed and developed as a potent and specific inhibitor of angiotensin-converting enzyme, a zinc metallopeptidase that participates in the synthesis of a hypertensive peptide, angiotensin II, and in the degradation of a hypotensive peptide, bradykinin. Earlier studies with a snake venom peptide (teprotride or SQ 20881) that could be administered only by injection demonstrated that specific inhibitors of angiotensin-converting enzyme could be highly effective as antihypertensive drugs, and helped to clarify the specificity and mechanism of action of the enzyme. A hypothetical model of the active center of angiotensin-converting enzyme based on its presumed analogy to the well characterized zinc metallopeptidase carboxypeptidase A was used to guide logical sequential improvements of a weakly active prototype inhibitor that led eventually to the highly optimized structure of captopril. The hypothetical working model of the active site of angiotensin-converting enzyme used to develop captopril continues to provide a firm basis for development of new types of specific inhibitors of this biologically important enzyme. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
