A precisely positioned chiral center in an i, i + 7 tether modulates the helicity of the backbone peptide

Kuan Hu; Chengjie Sun; Dan Yang; Yujie Wu; Chuan Shi; Longjian Chen; Tao Liao; Jialin Guo; Yinghuan Liu; Zigang Li

doi:10.1039/C7CC03799F

A precisely positioned chiral center in an i, i + 7 tether modulates the helicity of the backbone peptide†

Kuan Hu,

‡^a Chengjie Sun,‡^a Dan Yang,‡^a Yujie Wu,^b Chuan Shi,^a Longjian Chen,^a Tao Liao,^a Jialin Guo,^c Yinghuan Liu^a and Zigang Li*^a

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* Corresponding authors

^a School of Chemical Biology and Biotechnology, Shenzhen Graduate School of Peking University, Shenzhen, China
E-mail: lizg@pkusz.edu.cn

^b Department of Biology, Southern University of Science and Technology, Shenzhen, Guangdong, P. R. China

^c Shenzhen Senior High School, Shenzhen, China

Abstract

In some cases, helical peptides stabilized by an i, i + 7 tether exhibit better target binding and cellular functions compared to their i, i + 4 analogues. Herein, we carried out a systematic study of the effects of an in-tether chiral center on the i, i + 7 system. We screened the optimal cross linking mode, tether length, in-tether chiral center positions, and absolute configurations. From these studies, we determined that a chiral center of R absolute configuration at the γ-position to the C-terminal of a 10-membered tether could function to efficiently induce helicity of the backbone peptides. This is an important addition to the current i, i + 4 in-tether chiral center induced helicity strategy (CIH strategy), and could have broad biological applications.

Chemical Communications

A precisely positioned chiral center in an i, i + 7 tether modulates the helicity of the backbone peptide†

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A precisely positioned chiral center in an i, i + 7 tether modulates the helicity of the backbone peptide

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