Aza-peptide epoxides: a new class of inhibitors selective for clan CD cysteine proteases.
Aza-peptide epoxides, a new class of irreversible protease inhibitors, are specific for the clan CD cysteine proteases. The inhibitors have second-order rate constants up to 10(5) M(-1) s(-1), with the most potent epoxides having the S,S stereochemistry. The aza-Asn derivatives are effective legumain inhibitors, while the aza-Asp epoxides were specific for caspases. The inhibitors have little or no inhibition with other proteases such as chymotrypsin, papain, or cathepsin B.
Asgian
Juliana L
JL
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta 30332-0400, USA.
James
Karen Ellis
KE
Li
Zhao Zhao
ZZ
Carter
Wendy
W
Barrett
Alan J
AJ
Mikolajczyk
Jowita
J
Salvesen
Guy S
GS
Powers
James C
JC
D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D061945:Caspase Inhibitors; D002401:Cathepsin B / Q000037:antagonists & inhibitors; D018360:Crystallography, X-Ray; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D004852:Epoxy Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D007700:Kinetics; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D010206:Papain / Q000037:antagonists & inhibitors; D010940:Plant Proteins / Q000037:antagonists & inhibitors; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D000099240:Asparaginyl Endopeptidase
D001372:Aza Compounds; D061945:Caspase Inhibitors; D002401:Cathepsin B; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors; D004852:Epoxy Compounds; D009842:Oligopeptides; D010206:Papain; D010940:Plant Proteins; D000099240:Asparaginyl Endopeptidase