GLP-1 Val8: A Biased GLP-1R Agonist with Altered Binding Kinetics and Impaired Release of Pancreatic Hormones in Rats.
Journal
ACS pharmacology & translational science
ISSN: 2575-9108
Titre abrégé: ACS Pharmacol Transl Sci
Pays: United States
ID NLM: 101721411
Informations de publication
Date de publication:
12 Feb 2021
12 Feb 2021
Historique:
received:
12
11
2020
entrez:
22
2
2021
pubmed:
23
2
2021
medline:
23
2
2021
Statut:
epublish
Résumé
Biased ligands that selectively confer activity in one pathway over another are pharmacologically important because biased signaling may reduce on-target side effects and improve drug efficacy. Here, we describe an N-terminal modification in the incretin hormone glucagon-like peptide (GLP-1) that alters the signaling capabilities of the GLP-1 receptor (GLP-1R) by making it G protein biased over internalization but was originally designed to confer DPP-4 resistance and thereby prolong the half-life of GLP-1. Despite similar binding affinity, cAMP production, and calcium mobilization, substitution of a single amino acid (Ala8 to Val8) in the N-terminus of GLP-1(7-36)NH
Identifiants
pubmed: 33615180
doi: 10.1021/acsptsci.0c00193
pmc: PMC7887852
doi:
Types de publication
Journal Article
Langues
eng
Pagination
296-313Informations de copyright
© 2021 American Chemical Society.
Déclaration de conflit d'intérêts
The authors declare no competing financial interest.
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