Synthesis of dipeptide-bound epoxides and alpha,beta-unsaturated amides as potential irreversible transglutaminase inhibitors.
Herein we report the synthesis of 24 novel peptides as potential irreversible inactivators of transglutaminase (TGase). These peptides were designed to resemble Cbz-L-Gln-Gly, known to be a good TGase substrate, and to include either alpha,beta-unsaturated amide groups or the corresponding epoxide groups. The side chain length of the amino acid residue bearing the inhibitor group was also varied in order to permit investigation of this effect.
de Macédo
Pierre
P
Département de chimie, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, H3C 3J7, Québec, Canada.
Marrano
Claudio
C
Keillor
Jeffrey W
JW
D000577:Amides / Q000737:chemistry; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D013329:Structure-Activity Relationship; D011503:Transglutaminases / Q000037:antagonists & inhibitors*
D000577:Amides; D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D010455:Peptides; D011503:Transglutaminases