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Targeting GLP-1 receptor trafficking to improve agonist efficacy.
Jones B, Buenaventura T, Kanda N, Chabosseau P, Owen BM, Scott R, Goldin R, Angkathunyakul N, Corrêa IR Jr, Bosco D, Johnson PR, Piemonti L, Marchetti P, Shapiro AMJ, Cochran BJ, Hanyaloglu AC, Inoue A, Tan T, Rutter GA, Tomas A, Bloom SR. Jones B, et al. Nat Commun. 2018 Apr 23;9(1):1602. doi: 10.1038/s41467-018-03941-2. Nat Commun. 2018. PMID: 29686402 Free PMC article.
Glucagon-like peptide-1 receptor (GLP-1R) activation promotes insulin secretion from pancreatic beta cells, causes weight loss, and is an important pharmacological target in type 2 diabetes (T2D). Like other G protein-couple
Glucagon-like peptide-1 receptor (GLP-1R) activation promotes insulin secretion from pancreatic be
Ureidopeptide GLP-1 analogues with prolonged activity in vivo via signal bias and altered receptor trafficking.
Fremaux J, Venin C, Mauran L, Zimmer R, Koensgen F, Rognan D, Bitsi S, Lucey MA, Jones B, Tomas A, Guichard G, Goudreau SR. Fremaux J, et al. Chem Sci. 2019 Sep 11;10(42):9872-9879. doi: 10.1039/c9sc02079a. eCollection 2019 Nov 14. Chem Sci. 2019. PMID: 32015811 Free PMC article.
Based on molecular dynamics simulations, N-terminally modified GLP-1 analogues with a ureido residue replacement at position 2 were synthesized and showed preservation of agonist activity while exhibiting a substantial increase in stability. This enabling pla …
Based on molecular dynamics simulations, N-terminally modified GLP-1 analogues with a ureido residue replacement at position 2 …