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用于模拟或破坏蛋白质-蛋白质相互作用的β-转角类似物的固相合成。

Solid-phase syntheses of beta-turn analogues to mimic or disrupt protein-protein interactions.

作者信息

Burgess K

机构信息

Chemistry Department, Texas A & M University, Box 30012, College Station, Texas 77842-3012, USA.

出版信息

Acc Chem Res. 2001 Oct;34(10):826-35. doi: 10.1021/ar9901523.

Abstract

Protein-protein interactions are difficult targets in medicinal chemistry, but they will become increasingly important as data from The Human Genome Project is interpreted. Our work focuses on beta-turn mimics that are designed to mimic or disrupt some of these interactions. Solid-phase syntheses and preferred conformations of beta-turn mimics that incorporate dipeptide units are discussed. The activity of one illustrative compound that potentiates the interaction of the nerve growth factor with its transmembrane tyrosine kinase receptor TrkA is outlined. Finally, the importance of dimeric turn mimics and some new approaches to these are described.

摘要

蛋白质-蛋白质相互作用是药物化学中难以攻克的靶点,但随着人类基因组计划数据的解读,它们将变得越来越重要。我们的工作重点是β-转角模拟物,其设计目的是模拟或破坏其中一些相互作用。本文讨论了包含二肽单元的β-转角模拟物的固相合成及其优势构象。概述了一种具有代表性的化合物的活性,该化合物可增强神经生长因子与其跨膜酪氨酸激酶受体TrkA之间的相互作用。最后,描述了二聚体转角模拟物的重要性以及针对它们的一些新方法。

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