HIS REPORTER DISPLACEMENT ASSAY FOR FRAGMENT SCREENING AND FRAGMENT EVOLUTION TOWARD LEADS WITH OPTIMIZED BINDING KINETICS, BINDING SELECTIVITY, AND THERMODYNAMIC SIGNATURE

被引：47

作者：

Neumann, Lars ^{[1
]}

von Koenig, Konstanze ^{[1
]}

Ullmann, Dirk ^{[1
]}

机构：

[1] Proteros Biostruct GmbH, Martinsried, Germany

来源：

FRAGMENT-BASED DRUG DESIGN: TOOLS, PRACTICAL APPROACHES, AND EXAMPLES | 2011年 / 493卷

关键词：

ACTIVATED PROTEIN-KINASE; RESIDENCE TIME; DRUG; TECHNOLOGY; DISCOVERY; BIOSENSOR; ENTHALPY; RECEPTOR; ENTROPY;

D O I：

10.1016/B978-0-12-381274-2.00012-1

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Parameters such as residence time, kinetic selectivity, and thermodynamic signature are more and more under debate as optimization objectives within fragment-based lead discovery. However, broad implementation of these parameters is hampered by the lack of technologies that give rapid access to binding kinetics and thermodynamic information for large amounts of compound-target interactions. Here, the authors describe a technology the reporter displacement assay that is capable of opening this bottleneck and of supporting data-driven design of lead compounds with tailor-made residence time, kinetic selectivity, and thermodynamic signature.

引用

页码：299 / 320

页数：22

共 28 条

[1]

[Anonymous], CURR OPIN STRUCT BIO

[2] Calorimetry and thermodynamics in drug design [J].