Synthesis and evaluation of novel dipeptide-bound 1,2,4-thiadiazoles as irreversible inhibitors of guinea pig liver transglutaminase

Herein we report the synthesis and evaluation of 14 novel peptides as poten tial irreversible inactivators of guinea pig liver transglutaminase (TGase) . These peptides were designed to resemble Cbz-L-Gln-Gly, known to be a goo d 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 vari ed in order to permit investigation of this effect. Their inactivation rate constants were measured using a direct continuous spectrophotometric metho d and were found to vary between 0.330 to 0.89 muM min(-1). (C) 2001 Elsevi er Science Ltd. All rights reserved.