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An In‐tether Chiral Center Modulates the Helicity, Cell Permeability, and Target Binding Affinity of a Peptide
Author(s) -
Hu Kuan,
Geng Hao,
Zhang Qingzhou,
Liu Qisong,
Xie Mingsheng,
Sun Chengjie,
Li Wenjun,
Lin Huacan,
Jiang Fan,
Wang Tao,
Wu YunDong,
Li Zigang
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201602806
Subject(s) - circular dichroism , peptide , diastereomer , chemistry , helicity , stereochemistry , nuclear magnetic resonance spectroscopy , crystallography , chirality (physics) , biophysics , biochemistry , physics , biology , chiral symmetry , nambu–jona lasinio model , particle physics , quantum mechanics , quark
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.