Novel diphenyl esters of peptidyl α-aminoalkylphosphonates as inhibitors of chymotrypsin and subtilisin

Abstract

The activities of novel Cbz-N-protected α-aminophosphonic phenyl esters, analogs of leucine (115) and phenylalanine (1729), which are substituted at the phenyl ester rings, as well as of their peptidic derivatives (3143), were investigated for their inhibitory effects on chymotrypsin and subtilisin. The chemical nature and position of the examined substituents clearly demonstrated a strong structureactivity relationship. Among all synthesized compounds the most potent phosphonic-type inhibitors of subtilisin and chymotrypsin were identified, with k2/Ki values 114,380M-1s -1 and 307,380M-1s-1, respectively. © 2009 Informa UK Ltd.