Synthesis and evaluation of peptidic maleimides as transglutaminase inhibitors.
A series of novel transglutaminase inhibitors was prepared, based on the scaffold of a commonly used peptide substrate and bearing an electrophilic maleimide group. These compounds were evaluated in vitro and shown to lead to irreversible inactivation of tissue transglutaminase. Comparison with inhibitors studied previously provides insight into the steric environment of the enzyme active site.
Halim
Dany
D
Département de chimie, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, Que., Canada H3C 3J7.
Caron
Karine
K
Keillor
Jeffrey W
JW
D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D004926:Escherichia coli / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008301:Maleimides / Q000138:chemical synthesis* / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D011503:Transglutaminases / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D008301:Maleimides; D010455:Peptides; D011503:Transglutaminases