Research ArticleChemistry

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

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Science Advances  15 May 2020:
Vol. 6, no. 20, eaaz4988
DOI: 10.1126/sciadv.aaz4988

Abstract

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.

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