Molecular modelling of the rat peroxisome proliferator-activated receptor-α (rPPARα) by homology with the human retinoic acid X receptor α (hRXRα) and investigation of ligand binding interactions I:: QSARs

被引：17

作者：

Lewis, DFV ^{[1
]}

Lake, BG

机构：

[1] Univ Surrey, Sch Biol Sci, Mol Toxicol Grp, Guildford GU2 5XH, Surrey, England

[2] British Ind Biol Res Assoc, Carshalton SM5 4DS, Surrey, England

来源：

TOXICOLOGY IN VITRO | 1998年 / 12卷 / 06期

关键词：

peroxisome proliferator-activated receptor; molecular modelling; quantitative structure-activity relationships;

D O I：

10.1016/S0887-2333(98)00056-3

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

The construction of a homology model of the ligand binding domain of the rat peroxisome proliferator-activated receptor-alpha (rPPAR alpha) based on the crystal structure of the human retinoic acid X receptor-alpha (hRXR alpha) is reported. It is demonstrated that many known peroxisome proliferators are able to occupy the putative ligand binding site of the rPPAR alpha, including clofibric acid, ciprofibrate, nafenopin and related compounds. The log. relative potency of several peroxisome proliferators can be quantitatively related (R = 0.99) to their binding affinity and lipophilicity as measured by their distribution coefficients (logD(7.4) values) and other QSARs are discussed in the light of receptor-ligand interactions. The molecular modelling of a representative number of peroxisome proliferators within the putative ligand binding site is consistent with experimental information on relative potency and enantioselectivity. (C) 1998 Elsevier Science Ltd. All rights reserved.

引用

页码：619 / 632

页数：14

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