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Chiral Sulfoxide-Induced Single Turn Peptide α-Helicity.

ABSTRACT: Inducing α-helicity through side-chain cross-linking is a strategy that has been pursued to improve peptide conformational rigidity and bio-availability. Here we describe the preparation of small peptides tethered to chiral sulfoxide-containing macrocyclic rings. Furthermore, a study of structure-activity relationships (SARs) disclosed properties with respect to ring size, sulfur position, oxidation state, and stereochemistry that show a propensity to induce α-helicity. Supporting data include circular dichroism spectroscopy (CD), NMR spectroscopy, and a single crystal X-ray structure for one such stabilized peptide. Finally, theoretical studies are presented to elucidate the effect of chiral sulfoxides in inducing backbone α-helicity.

SUBMITTER: Zhang Q

PROVIDER: S-EPMC5146914 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Chiral Sulfoxide-Induced Single Turn Peptide α-Helicity.

Zhang Qingzhou Q Jiang Fan F Zhao Bingchuan B Lin Huacan H Tian Yuan Y Xie Mingsheng M Bai Guoyun G Gilbert Adam M AM Goetz Gilles H GH Liras Spiros S Mathiowetz Alan A AA Price David A DA Song Kun K Tu Meihua M Wu Yujie Y Wang Tao T Flanagan Mark E ME Wu Yun-Dong YD Li Zigang Z

Scientific reports 20161209

Inducing α-helicity through side-chain cross-linking is a strategy that has been pursued to improve peptide conformational rigidity and bio-availability. Here we describe the preparation of small peptides tethered to chiral sulfoxide-containing macrocyclic rings. Furthermore, a study of structure-activity relationships (SARs) disclosed properties with respect to ring size, sulfur position, oxidation state, and stereochemistry that show a propensity to induce α-helicity. Supporting data include c ...[more]

PMID: 27934919

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