Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA (UK) http://hamilton.chem.ox.ac.uk.
Angew Chem Int Ed Engl. 2015 Feb 23;54(9):2649-52. doi: 10.1002/anie.201410290. Epub 2015 Jan 19.
Many therapeutically relevant protein-protein interactions contain hot-spot regions on secondary structural elements, which contribute disproportionately to binding enthalpy. Mimicry of such α-helical regions has met with considerable success, however the analogous approach for the β-strand has received less attention. Presented herein is a foldamer for strand mimicry in which dipolar repulsion is a central determinant of conformation. Computation as well as solution- and solid-phase data are consistent with an ensemble weighted almost exclusively in favor of the desired conformation.
许多治疗相关的蛋白质-蛋白质相互作用包含二级结构元件上的热点区域，这些区域对结合焓的贡献不成比例。这种α-螺旋区域的模拟已经取得了相当大的成功，然而类似的β-折叠模拟方法却受到了较少的关注。本文介绍了一种用于链模拟的折叠体，其中偶极力是构象的主要决定因素。计算以及溶液和固相数据都与一个几乎完全有利于所需构象的集合相一致。
