Encounter with unexpected collagenase-1 selective inhibitor: Switchover of inhibitor binding pocket induced by fluorine atom

被引：12

作者：

Sawa, M

Kondo, H

Nishimura, S

机构：

[1] Nippon Organon KK, R&D Labs, Dept Chem, Miyakojima Ku, Osaka 5340016, Japan

[2] Hokkaido Univ, Grad Sch Sci, Div Biol Sci, Sapporo, Hokkaido 0600810, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 04期

关键词：

D O I：

10.1016/S0960-894X(01)00796-X

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Phosphonamide-based inhibitors having trifluoromethyl moiety showed highly selective inhibition against MMP-1. A possible mechanism of the selectivity of MMP-1 inhibitors through the switchover of the binding pocket was speculated by computational calculations. As a consequence of the unexpected selectivity, the specific interaction of CF3 group of the inhibitor and Arg214 in the S1' pocket of MMP-1 conducted a low binding energy. (C) 2002 Elsevier Science Ltd. All rights reserved.

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页码：581 / 584

页数：4

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