Design of conformationally constrained angiotensin-converting enzyme inhibitors.
Modification of alanyl proline by introduction of both zinc coordinating and S1 subsite binding interactions affords potent new carboxy- and mercapto-acyl dipeptide angiotensin-converting enzyme (ACE) inhibitors. Design of these inhibitors was guided by an extension of the hypothetical ACE active site model originally used to derive captopril. Significant increases in ACE inhibitory activity were observed by introduction of conformation constraint into acyclic acyl dipeptides, thus further defining the three dimensional structure of the ACE active site.
D000806:Angiotensin-Converting Enzyme Inhibitors; D001665:Binding Sites; D004151:Dipeptides / Q000032:analysis / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000032:analysis*; D008956:Models, Chemical; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D015032:Zinc / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D004791:Enzyme Inhibitors; D015032:Zinc