title: Thiazolidine derivatives as potent inhibitors specific for prolyl endopeptidase.
abstract: A series of N-blocked L-proline-containing compounds and their derivatives were synthesized. Their inhibitory activities for prolyl endopeptidase from bovine brain were examined and compared with that of N-benzyloxycarbonyl-L-prolyl-L-prolinal, which is the most effective enzyme inhibitor hitherto reported. Introduction of a sulfur atom into pyrrolidine ring quite effectively increased the inhibitory activity: replacement of pyrrolidine with thiazolidine or thiazolidine aldehyde (thioprolinal) and conversion of L-proline to L-thioproline residue resulted in increase in the inhibitory activity. Thus, N-benzyloxycarbonyl-L-thioprolyl-thiazolidine (Z-Thiopro-thiazolidine) and Z-L-Thiopro-L-thioprolinal showed Ki values of 0.36 and 0.01 nM, respectively, for prolyl endopeptidase from bovine brain; both values were significantly lower than that of Z-Pro-prolinal (Ki, 3.7 nM).
authors.affiliation: School of Pharmaceutical Sciences, Nagasaki University.
authors.forename: D
authors.initials: D
authors.lastname: Tsuru
authors.forename: T
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: N
authors.initials: N
authors.lastname: Koriyama
authors.forename: S
authors.initials: S
authors.lastname: Furukawa
mesh_terms: D010450:Endopeptidases; D015394:Molecular Structure; D000085822:Prolyl Oligopeptidases; D011480:Protease Inhibitors; D012697:Serine Endopeptidases; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D011480:Protease Inhibitors; D013844:Thiazoles; D010450:Endopeptidases; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases