title: Synthesis and evaluation of novel dipeptide-bound 1,2,4-thiadiazoles as irreversible inhibitors of guinea pig liver transglutaminase.
abstract: Herein we report the synthesis and evaluation of 14 novel peptides as potential irreversible inactivators of guinea pig liver transglutaminase (TGase). These peptides were designed to resemble Cbz-L-Gln-Gly, known to be a good TGase substrate, and to include a 1,2,4-thiadiazole group. The side chain length of the amino acid residue bearing the inhibitor group was also varied in order to permit investigation of this effect. Their inactivation rate constants were measured using a direct continuous spectrophotometric method and were found to vary between 0.330 to 0.89 microM(-1) min(-1).
authors.affiliation: Département de chimie, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, Québec, Canada H3C 3J7.
authors.forename: C
authors.initials: C
authors.lastname: Marrano
authors.forename: P
authors.initials: P
authors.lastname: de Macédo
authors.forename: P
authors.initials: P
authors.lastname: Gagnon
authors.forename: D
authors.initials: D
authors.lastname: Lapierre
authors.forename: C
authors.initials: C
authors.lastname: Gravel
authors.forename: J W
authors.initials: JW
authors.lastname: Keillor
mesh_terms: D000818:Animals; D001671:Biochemistry / Q000379:methods; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006168:Guinea Pigs; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D010455:Peptides / Q000737:chemistry; D013329:Structure-Activity Relationship; D011503:Transglutaminases / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D010455:Peptides; D011503:Transglutaminases