Modeling cyclooxygenase inhibition.: Implication of active site hydration on the selectivity of ketoprofen analogues

被引:51
作者
Palomer, A
Pérez, JJ
Navea, S
Llorens, O
Pascual, J
García, L
Mauleón, D
机构
[1] Labs Menarini, R&D Dept, Badalona 08918, Spain
[2] UPC, ETSEIB, Dept Engn Quim, Barcelona 08028, Spain
关键词
D O I
10.1021/jm9906217
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Molecular modeling studies performed on the two cyclooxygenase isozymes (COXs) suggest that active site hydration is crucial for understanding inhibitor selectivity. In this work, models have been constructed considering some implicit water molecules, placed in the position suggested by GRID, that participate in the dynamic hydrogen-bonding network at the polar active site entrance together with protein residues 355, 524, 120, and 513. The selectivity observed for ketoprofen (1) and the structural analogues 2 and 3 may be rationalized in terms of such implicit hydration.
引用
收藏
页码:2280 / 2284
页数:5
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