An In-tether Chiral Center Modulates the Helicity, Cell Permeability, and Target Binding Affinity of a Peptide

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• 作者：Kuan Hu ; Hao Geng ; Qingzhou Zhang ; Qisong Liu ; Mingsheng Xie ; Chengjie Sun ; Wenjun Li ; Huacan Lin ; Dr. Fan Jiang ; Prof. Tao Wang ; Prof. Yun-Dong Wu and Prof. Zigang Li
• 刊名：Angewandte Chemie
• 出版年：2016
• 出版时间：July 4, 2016
• 年：2016
• 卷：128
• 期：28
• 页码：8145-8149
• 全文大小：3177K
• ISSN：1521-3757

文摘

The addition of a precisely positioned chiral center in the tether of a constrained peptide is reported, yielding two separable peptide diastereomers with significantly different helicity, as supported by circular dichroism (CD) and NMR spectroscopy. Single crystal X-ray diffraction analysis suggests that the absolute configuration of the in-tether chiral center in helical form is R, which is in agreement with theoretical simulations. The relationship between the secondary structure of the short peptides and their biochemical/biophysical properties remains elusive, largely because of the lack of proper controls. The present strategy provides the only method for investigating the influence of solely conformational differences upon the biochemical/biophysical properties of peptides. The significant differences in permeability and target binding affinity between the peptide diastereomers demonstrate the importance of helical conformation.