Implications of protein flexibility for drug discovery

被引：572

作者：

Teague, SJ ^{[1
]}

机构：

[1] AstraZeneca R&D Charnwood, Loughborough LE11 5RH, Leics, England

来源：

NATURE REVIEWS DRUG DISCOVERY | 2003年 / 2卷 / 07期

关键词：

D O I：

10.1038/nrd1129

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Proteins are in constant motion between different conformational states with similar energies. This has often been ignored in drug design. However, protein flexibility is fundamental to understanding the ways in which drugs exert biological effects, their binding-site location, binding orientation, binding kinetics, metabolism and transport. Protein flexibility allows increased affinity to be achieved between a drug and its target. This is crucial, because the lipophilicity and number of polar interactions allowed for an oral drug is limited by absorption, distribution, metabolism and toxicology considerations.

引用

页码：527 / 541

页数：15

共 94 条

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