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Highly potent and selective 4,4'‐biphenyl‐4‐acylate‐4'‐ N ‐ n ‐butylcarbamate inhibitors of Pseudomonas species lipase
Author(s) -
Lin Gialih,
Chen GanHong,
Lin YanFu,
Su LiHsiang,
Liao PeiShin
Publication year - 2005
Publication title -
european journal of lipid science and technology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.614
H-Index - 94
eISSN - 1438-9312
pISSN - 1438-7697
DOI - 10.1002/ejlt.200401050
Subject(s) - stereochemistry , chemistry , substituent , moiety , steric effects , biphenyl , lipase , enzyme , active site , biochemistry , organic chemistry
4,4'‐Biphenyl‐4‐acylate‐4'‐ N ‐ n ‐butylcarbamates ( 1–8 ) are synthesized and characterized as highly potent and selective pseudo‐substrate inhibitors of Pseudomonas species lipase. Thus, the n ‐butylcarbamate moieties of the inhibitors bind to the first acyl chain binding site (ACS) of the enzyme. Therefore, the ester moieties of the inhibitors may bind to the second ACS of the enzyme, due to the linear 4,4'‐biphenyl moiety of the inhibitors. –log K i , log k 2 , and log k i values of carbamates 1–8 are multiply linearly correlated with the Taft steric constant ( E S ) and the Hansch hydrophobicity constant (π), but not with the Taft substituent constant (σ*). For –log K i , log k 2 , and log k i correlations, values of δ are 0.8, 0.34, and 1.0, respectively, and values of ψ are 1.0, 0.4, and 1.3, respectively. Positive δ and ψ values for these correlations indicate that the second ACS of the enzyme prefers to bind to small and hydrophobic ester groups of the inhibitors. Among carbamates 1–8 , carbamate 3 , with a K i value of 2.5 nM, is the most potent inhibitor.