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The activity of sulfono-?-AApeptide helical foldamers that mimic GLP-1.

ABSTRACT: Existing long ?-helix mimicking necessitates the retention of most natural amino acid residues to maintain their biological activity. Here, we report the exploration of helical sulfono-?-AApeptides with entire unnatural backbones for their ability to structurally and functionally mimic glucagon-like peptide 1 (GLP-1). Our findings suggest that efficient construction of novel GLP-1 receptor (GLP-1R) agonists could be achieved with nanomolar potencies. In addition, the resulting sulfono-?-AApeptides were also proved to display remarkable stability against enzymatic degradation compared to GLP-1, augmenting their biological potential. This alternative strategy of ?-helix mimicking, as a proof of concept, could provide a new paradigm to prepare GLP-1R agonists.

SUBMITTER: Sang P

PROVIDER: S-EPMC7228743 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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The activity of sulfono-γ-AApeptide helical foldamers that mimic GLP-1.

Sang Peng P Zhou Zhihong Z Shi Yan Y Lee Candy C Amso Zaid Z Huang David D Odom Timothy T Nguyen-Tran Vân T B VTB Shen Weijun W Cai Jianfeng J

Science advances 20200515 20

Existing long α-helix mimicking necessitates the retention of most natural amino acid residues to maintain their biological activity. Here, we report the exploration of helical sulfono-γ-AApeptides with entire unnatural backbones for their ability to structurally and functionally mimic glucagon-like peptide 1 (GLP-1). Our findings suggest that efficient construction of novel GLP-1 receptor (GLP-1R) agonists could be achieved with nanomolar potencies. In addition, the resulting sulfono-γ-AApeptid ...[more]

PMID: 32440547

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