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

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...

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Bibliographic Details
Published in:Science advances 2020-05, Vol.6 (20), p.eaaz4988-eaaz4988
Main Authors: Sang, Peng, Zhou, Zhihong, Shi, Yan, Lee, Candy, Amso, Zaid, Huang, David, Odom, Timothy, Nguyen-Tran, Vân T B, Shen, Weijun, Cai, Jianfeng
Format: Article
Language:English
Subjects:
Chemistry
Glucagon-Like Peptide 1
Organic Chemistry
Peptides - chemistry
Peptidomimetics - chemistry
Protein Conformation, alpha-Helical
SciAdv r-articles
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Summary: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-AApeptides were also proved to display remarkable stability against enzymatic degradation compared to GLP-1, augmenting their biological potential. This alternative strategy of α-helix mimicking, as a proof of concept, could provide a new paradigm to prepare GLP-1R agonists.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.aaz4988