Similarities of the substrate cleavage catalyzed by proline specific endopeptidase and dipeptidyl peptidase IV

Abstract

Sixteen substrates of the type succinyl-Ala-Ala-pX-anilide and succinyl-Ala-Pro-pX anilide having different substituents (X) in p-position of the aryl residue were synthesized and characterized. The influence of electronic as well as hydrophobic substituent consts., s and p, on the hydrolysis of substrates catalyzed by proline-specific endopeptidase (PSE) was investigated. In the Hansch approach, the catalytic consts. log kcat and log (kcat/Km) of succinyl-Ala-Ala-pX-anilides hydrolyzed by PSE correlate significantly with electronic substituent consts. s, whereas there is no correlation in the case of succinyl-Ala-Pro-pX-anilides. The intercorrelation data from dipeptidyl peptidase IV-catalyzed hydrolysis of Ala-Ala-pX-anilides suggest that both enzymes act by a similar catalytic mechanism.