R. Joyeau et al., Synthesis and activity of pyrrolidinyl- and thiazolidinyl-dipeptide derivatives as inhibitors of the Tc80 prolyl oligopeptidase from Trypanosoma cruzi, EUR J MED C, 35(2), 2000, pp. 257-266
Pyrrolidinyl- and thiazolidinyl- dipeptide derivatives, featuring either a
vinyl sulfone-, a 2-ketobenzothiazole-, a nitrile-, or a benzimidazole grou
p at the C-terminus, were designed and synthesized as potential inhibitors
of the prolyl-specific Tc80 proteinase from Trypanosoma cruzi, the agent of
Chagas' disease. These compounds were evaluated in vitro towards the targe
t enzyme which was classified as a serine protease belonging to the prolyl
oligopeptidase family (EC 3.4.21.26). A peptidyl nitrile and two peptidyl a
lpha-ketobenzothiazoles were shown to be potent reversible and competitive
inhibitors of Tc 80 proteinase, with K-i values in the range 38-219 nM, and
compared advantageously with some known mammalian prolyl oligopeptidase in
hibitors. (C) 2000 Editions scientifiques et medicales Elsevier SAS.