Peptidase-catalyzed formation of macrocyclic lactams on solid phase identifies ring systems thatare favorably bound in the enzyme active site. We evaluated several cyclic peptide motifs lin
kedby ester bonds between the P2 and P1' or the P1 and P2' side chains. The depsipeptide representedby structure
5 was readily generated by a variety of peptidases from precursor
![](/images/gifchars/omega.gif)
-amino acids or
![](/images/gifchars/omega.gif)
-amino esters. This strategy for identifying ring systems for potential macrocyclic transition stateanalogues was demonstrated with the serine peptidases trypsin and chymotrypsin, with the asparticpeptidase pepsin, and with the zinc peptidase thermolysin.