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標題: QSAR for phospholipase A(2) inhibitions by 1-acyloxy-3-N-n-octylcarbamyl-benzenes
作者: Lin, G.L.
Yu, G.Y.
關鍵字: phospholipase A(2);QSAR;enzyme mechanism;carbamate inhibitor;structure-reactivity relationships;cross-interaction correlations;transition-state analog;pancreatic cholesterol esterase;acetylcholinesterase inhibition;elementary processes;benzeneboronic;acid;mechanisms;probes;protease
Project: Bioorganic & Medicinal Chemistry Letters
期刊/報告no:: Bioorganic & Medicinal Chemistry Letters, Volume 15, Issue 9, Page(s) 2405-2408.
1-Acyloxy-3-N-n-octylcarbamyl-benzenes are potent reversible competitive inhibitors of Naja mocambique mocambique phospholipase A(2) with the K-i values from 9.6 to 119 μ M. The pK(i) values are correlated to both Taft substituent constant σ(*) and Hansch hydrophobicity constant π. The pre-steady state inhibition studies indicate that the pK(s) values for the first inhibition step are linearly correlated to σ(*) alone with the p(*) of -0.09 for this correlation. Thus, the first inhibition step may involve the insertion of the inhibitor to hepta-coordinated Ca2+ ion of the enzyme to form the octa-coordinated Ca2+ ion of the enzyme. The log(k(2)/k(-2)) values for the second inhibition step are linearly correlated to 71 alone, and the ψ value for this correlation is 0.13. Therefore, the second step inhibition step may involve the van der Waals' interaction between the acyl group of the inhibitor and Tyr 69 of the enzyme. © 2005 Elsevier Ltd. All rights reserved.
ISSN: 0960-894X
DOI: 10.1016/j.bmcl.2005.02.092
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