Irreversible inhibition of zinc-containing protease by oxazolidinone derivatives. Novel inactivation chemistry.
alpha-Benzyl-2-oxo-1,3-oxazolidine-4-acetic acid (BOOA) having (alpha R,4S) and (alpha S,4R) configurations were designed and synthesized as a novel type of mechanism-based inactivators for carboxypeptidase A (CPA), and kinetic analysis demonstrated that they indeed inhibit the enzyme in a time-dependent manner with the second order inhibitory rate constants (kinact/KI) of 1.52 and 1.39 M-1 s-1 for (alpha S,R4)-BOOA and (alpha R,4S)-BOOA, respectively.
Kim
D H
DH
Center for Biofunctional Molecules, Pohang University of Science and Technology, Korea.
Chung
S J
SJ
Kim
E J
EJ
Tian
G R
GR
D002268:Carboxypeptidases / Q000037:antagonists & inhibitors*; D043422:Carboxypeptidases A; D015195:Drug Design; D007700:Kinetics; D015394:Molecular Structure; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010666:Phenylpropionates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D015032:Zinc
D010080:Oxazoles; D010666:Phenylpropionates; D011480:Protease Inhibitors; C116627:alpha-benzyl-2-oxo-1,3-oxazolidine-4-acetic acid; D002268:Carboxypeptidases; D043422:Carboxypeptidases A; D015032:Zinc