1. An In-tether Chiral Center Modulates the Helicity, Cell Permeability, and Target Binding Affinity of a Peptide.
- Author
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Hu, Kuan, Geng, Hao, Zhang, Qingzhou, Liu, Qisong, Xie, Mingsheng, Sun, Chengjie, Li, Wenjun, Lin, Huacan, Jiang, Fan, Wang, Tao, Wu, Yun ‐ Dong, and Li, Zigang
- Subjects
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MOLECULAR structure of peptides , *HELICITY (Chemistry) , *PERMEABILITY , *CHIRALITY , *DIASTEREOISOMERS , *PROTEIN-protein interactions - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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