Design and Structure of Stapled Peptides Binding to Estrogen Receptors

作者：Chris Phillips, Lee R. Roberts, Markus Schade, Richard Bazin, Andrew F. Bent, Nichola L. Davies, Rob Moore, Andrew Pannifer, Andrew R. Pickford, Stephen H. Prior, Christopher M. Read, Andrew D. Scott, David G. Brown, Bin Xu, Stephen L. Irving · 发表于：Journal of the American Chemical Society · 年份：2011 · DOI：10.1021/ja202946k · 被引用次数：249 · 研究领域：Estrogen and related hormone effects、Chemical Synthesis and Analysis、Computational Drug Discovery Methods

Synthetic peptides that specifically bind nuclear hormone receptors offer an alternative approach to small molecules for the modulation of receptor signaling and subsequent gene expression. Here we describe the design of a series of novel stapled peptides that bind the coactivator peptide site of estrogen receptors. Using a number of biophysical techniques, including crystal structure analysis of receptor-stapled peptide complexes, we describe in detail the molecular interactions and demonstrate that all-hydrocarbon staples modulate molecular recognition events. The findings have implications for the design of stapled peptides in general.