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朝着具有支架多样性和构象约束的寡聚物的浩瀚文库发展。

Towards vast libraries of scaffold-diverse, conformationally constrained oligomers.

机构信息

Departments of Chemistry and Cancer Biology, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA.

出版信息

Chem Commun (Camb). 2016 May 4;52(36):6038-59. doi: 10.1039/c6cc00617e. Epub 2016 Mar 21.

Abstract

There is great interest in the development of probe molecules and drug leads that would bind tightly and selectively to protein surfaces that are difficult to target with traditional molecules, such as those involved in protein-protein interactions. The currently available evidence suggests that this will require molecules that are larger and have quite different chemical properties than typical Lipinski-compliant molecules that target enzyme active sites. We describe here efforts to develop vast libraries of conformationally constrained oligomers as a potentially rich source of these molecules.

摘要

人们对于开发探针分子和药物先导物非常感兴趣,这些分子能够与传统分子难以靶向的蛋白质表面(如涉及蛋白质-蛋白质相互作用的表面)紧密且选择性地结合。目前的证据表明,这将需要比传统靶向酶活性位点的 Lipinski 合规分子更大且具有截然不同化学性质的分子。我们在这里描述了开发构象受限的寡聚物文库的努力,这是这些分子的潜在丰富来源。

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