Peptidyl and azapeptidyl methylketones as substrate analog inhibitors of papain and cathepsin B

R Calabretta, C Giordano, C Gallina, V Morea…

Index: Calabretta, R.; Giordano, C.; Gallina, C.; Morea, V.; Consalvi, V.; Scandurra, R. European Journal of Medicinal Chemistry, 1995 , vol. 30, # 12 p. 931 - 942

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Citation Number: 22

Abstract

Peptidyl methylketones containing Phe, Tyr, Tyr (I), Tyr (I2), Leu and Ile in P2 were synthesized and tested as substrate analog reversible inhibitors of papain and bovine spleen cathepsin B. The most effective cathepsin B inhibitor contained Tyr (I2) and displayed an inhibition constant of 4.7 μM at pH 6.8 and 25° C, while Leu or Ile gave practically inert analogs. Replacement of the amino acids in P2 with the analogous α-azaamino acids, as ...