Design of potent and specific inhibitors of carboxypeptidases A and B.
The combination in one molecule of functional groups that can interact specifically with different substrate binding areas at the active site of carboxypeptidases A and B has led to the development of potent and specific inhibitors of these enzymes. 2-Benzyl-3-mercaptopropanoic acid (SQ 14,603) has a Ki of 1.1 x 10(-8) M vs. carboxypeptidase A and a Ki of 1.6 x 10(-4) M vs. the B enzyme. 2-Mercaptomethyl-5-guanidinopentanoic acid (SQ 24,798) has a Ki of 4 x 10(-10) M vs. carboxypeptidase B and a Ki of 1.2 x 10(-5) M vs. carboxypeptidase A. It is proposed that the sulfhydryl groups of these inhibitors bind to the catalytically important zinc ions of these enzymes, and that, in conjunction with the benzyl and guanidinopropyl side chains, they are responsible for their specificity.
D015097:3-Mercaptopropionic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D001665:Binding Sites; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors*; D006146:Guanidines / Q000494:pharmacology; D007700:Kinetics; D008722:Methods; D011480:Protease Inhibitors / Q000138:chemical synthesis; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds
D006146:Guanidines; D011480:Protease Inhibitors; D013438:Sulfhydryl Compounds; C019268:2-benzyl-3-mercaptopropanoic acid; C028266:2-mercaptomethyl-5-guanidinopentanoic acid; D015097:3-Mercaptopropionic Acid; D002268:Carboxypeptidases