Conformationally constrained renin inhibitory peptides: .gamma.-lactam-bridged dipeptide isostere as conformational restriction
- 1 July 1988
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 31 (7) , 1369-1376
- https://doi.org/10.1021/jm00402a021
Abstract
A model of the conformation of the enzyme-bound inhibitor of human renin suggested the possibility of a .gamma.-lactam conformational restriction of the P2-P3 site. Synthetic routes to these .gamma.-lactam peptide isosteres and their incorporation into potential renin inhibitors are described. Peptide VIa,b with a .gamma.-lactam confornational constraint and a hydroxyethylene isostere at the cleavage site inhibited human plasma renin with an IC50 value of 6.5 nM. The flexibility of these eyntheses should make available a number of potential enzyme inhibitors with this structural feature for the study of enzyme-bound conformers.This publication has 5 references indexed in Scilit:
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