PT  - JOURNAL ARTICLE
AU  - Sang, Peng
AU  - Zhou, Zhihong
AU  - Shi, Yan
AU  - Lee, Candy
AU  - Amso, Zaid
AU  - Huang, David
AU  - Odom, Timothy
AU  - Nguyen-Tran, Vân T.B.
AU  - Shen, Weijun
AU  - Cai, Jianfeng
TI  - The activity of sulfono-γ-AApeptide helical foldamers that mimic GLP-1
AID  - 10.1126/sciadv.aaz4988
DP  - 2020 May 01
TA  - Science Advances
PG  - eaaz4988
VI  - 6
IP  - 20
4099  - http://advances.sciencemag.org/content/6/20/eaaz4988.short
4100  - http://advances.sciencemag.org/content/6/20/eaaz4988.full
SO  - Sci Adv2020 May 01; 6
AB  - 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.