Johnson, Lisa M.Barrick, StaceyHager, Marlies V.McFedries, AmandaHoman, Edwin A.Rabaglia, Mary E.Keller, Mark P.Attie, Alan D.Saghatelian, AlanBisello, AlessandroGellman, Samuel H.2015-10-012014Johnson, L. M., S. Barrick, M. Hager, A. McFedries, E. A. Homan, M. E. Rabaglia, M. P. Keller, et al. 2014. “A Potent α/β-Peptide Analogue of GLP-1 with Prolonged Action in Vivo.” Journal of the American Chemical Society 136 (37): 12848-12851. doi:10.1021/ja507168t. http://dx.doi.org/10.1021/ja507168t.0002-7863http://nrs.harvard.edu/urn-3:HUL.InstRepos:22856917Glucagon-like peptide-1 (GLP-1) is a natural agonist for GLP-1R, a G protein-coupled receptor (GPCR) on the surface of pancreatic β cells. GLP-1R agoinsts are attractive for treatment of type 2 diabetes, but GLP-1 itself is rapidly degraded by peptidases in vivo. We describe a design strategy for retaining GLP-1-like activity while engendering prolonged activity in vivo, based on strategic replacement of native α residues with conformationally constrained β-amino acid residues. This backbone-modification approach may be useful for developing stabilized analogues of other peptide hormones.en-USJournal Article2015-10-0110.1021/ja507168t