RT Journal Article
SR Electronic
T1 The activity of sulfono-γ-AApeptide helical foldamers that mimic GLP-1
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eaaz4988
DO 10.1126/sciadv.aaz4988
VO 6
IS 20
A1 Sang, Peng
A1 Zhou, Zhihong
A1 Shi, Yan
A1 Lee, Candy
A1 Amso, Zaid
A1 Huang, David
A1 Odom, Timothy
A1 Nguyen-Tran, Vân T.B.
A1 Shen, Weijun
A1 Cai, Jianfeng
YR 2020
UL http://advances.sciencemag.org/content/6/20/eaaz4988.abstract
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.