A Fragment??Based In Situ Combinatorial Approach To Identify High??Affinity Ligands for Unknown Binding Sites

…, X Jiang, H Koliwer??Brandl, DS Strasser…

Index: Shelke, Sachin V.; Cutting, Brian; Jiang, Xiaohua; Koliwer-Brandl, Hendrik; Strasser, Daniel S.; Schwardt, Oliver; Kelm, Soerge; Ernst, Beat Angewandte Chemie - International Edition, 2010 , vol. 49, # 33 p. 5721 - 5725

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Citation Number: 32

Abstract

With his publication “On the attribution and additivity of binding energies” in 1981, Jencks [1] launched a new area in medicinal chemistry, that is, the so-called fragment-based drug discovery (FBDD).[2] When fragments are linked, their individual binding energies are additive. In addition, because of the reduction of translational and rigid body rotational degrees of freedom, the entropy barrier is markedly lowered.[3] Thus, by linking two low- ...