Design and synthesis of dipeptidyl alpha',beta'-epoxy ketones, potent irreversible inhibitors of the cysteine protease cruzain.
The dipeptidyl epoxy ketone 4 is a potent, irreversible inhibitor of cruzain, a cysteine protease isolated from Trypanosoma cruzi, with an apparent second order inhibition rate constant of 330,000 sec-1M-1.
Roush
W R
WR
Department of Chemistry, University of Michigan, Ann Arbor 48109, USA.
González
F V
FV
McKerrow
J H
JH
Hansell
E
E
D003546:Cysteine Endopeptidases / Q000187:drug effects*; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D004151:Dipeptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D015195:Drug Design; D007659:Ketones / Q000138:chemical synthesis* / Q000494:pharmacology*; D007700:Kinetics; D015800:Protozoan Proteins / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D007659:Ketones; D015800:Protozoan Proteins; D003546:Cysteine Endopeptidases; C074032:cruzain, Trypanosoma cruzi