Reference : Synthesis, hydrolysis, biochemical and theoretical evaluation of 1,4-bis(alkoxycarbonyl)...
Scientific journals : Article
Physical, chemical, mathematical & earth Sciences : Chemistry
http://hdl.handle.net/2268/30029
Synthesis, hydrolysis, biochemical and theoretical evaluation of 1,4-bis(alkoxycarbonyl)azetidin-2-ones as potential elastase inhibitors
English
Gérard, Stéphane [ > > ]
Dive, Georges mailto [Université de Liège - ULg > > Centre d'ingénierie des protéines >]
Clamot, Brigitte [> > > >]
Touillaux, Roland [> > > >]
Marchand-Brynaert, Jacqueline [> > > >]
18-Mar-2002
Tetrahedron
Pergamon-Elsevier Science Ltd
58
12
2423-2433
Yes (verified by ORBi)
International
0040-4020
Oxford
[en] beta-lactam ; serine-protease inhibition ; elastase ; ab initio calculation
[en] A series of 1,4-bis(alkoxycarbonyl)azetidin-2-ones, designed as potential suicide-inhibitors of serine proteases, has been synthesized and evaluated against porcine pancreatic elastase (PPE). The most active compound (K(i)similar to10 muM; reversible inhibitor) was equipped with phenethyloxycarbonyl and benzyloxycarbonyl side-chains at positions N1 and C4, respectively, with the (S)-configuration. H-1 NMR spectroscopic analysis of the reaction mixtures showed that the ester function is preferentially hydrolyzed, in both chemical and enzyme-catalyzed reactions, with regard to the azetidinone and urethane functions. Considering the three potentially sensitive carbonyl functions and the two stereoisomers, ab initio calculations were performed to determine the energetic barriers required to reach the transition state structures of hydrolysis in a model of the enzyme pocket. (C) 2002 Elsevier Science Ltd. All rights reserved.
Researchers ; Professionals
http://hdl.handle.net/2268/30029

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