Adding calorimetric data to decision making in lead discovery: a hot tip

被引:291
作者
Ladbury, John E. [1 ]
Klebe, Gerhard [2 ]
Freire, Ernesto [3 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA
[2] Univ Marburg, Inst Pharmazeut Chem, D-635032 Marburg, Germany
[3] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA
关键词
ISOTHERMAL TITRATION CALORIMETRY; LIGAND EFFICIENCY; BINDING; AFFINITY; ENTHALPY; THROMBIN; OPTIMIZATION; INHIBITORS; PROTEINS; TRYPSIN;
D O I
10.1038/nrd3054
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
Recognition of the limitations of high-throughput screening approaches in the discovery of candidate drugs has reawakened interest in structure-based and other rational design methods. Here, we describe how isothermal titration calorimetry can be used to obtain thermodynamic data on the binding of compounds to protein targets. We propose that these data - particularly the change in enthalpy - could provide a valuable, complementary addition to established tools for selecting compounds in lead discovery and for aiding lead optimization.
引用
收藏
页码:23 / 27
页数:5
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