CCR2: characterization of the antagonist binding site from a combined receptor modeling/mutagenesis approach

TA Berkhout, FE Blaney, AM Bridges…

Index: Berkhout, Theo A.; Blaney, Frank E.; Bridges, Angela M.; Cooper, David G.; Forbes, Ian T.; Gribble, Andrew D.; Groot, Pieter H. E.; Hardy, Adam; Ife, Robert J.; Kaur, Rejbinder; Moores, Kitty E.; Shillito, Helen; Willetts, Jennifer; Witherington, Jason Journal of Medicinal Chemistry, 2003 , vol. 46, # 19 p. 4070 - 4086

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Citation Number: 98

Abstract

We describe here a classical molecular modeling exercise that was carried out to provide a basis for the design of novel antagonist ligands of the CCR2 receptor. Using a theoretical model of the CCR2 receptor, docking studies were carried out to define plausible binding modes for the various known antagonist ligands, including our own series of indole piperidine compounds. On the basis of these results, a number of site-directed mutations ( ...