Multifunctional Antibody Agonists Targeting Glucagon-like Peptide-1, Glucagon, and Glucose-Dependent Insulinotropic Polypeptide Receptors

Autor:	Van Nguyen-Tran, Huafei Zou, Elizabeth Chao, Jose Gonzalez, Danling Wang, Weijun Shen, Yuhan Zhang, Peter G. Schultz, Peng-Yu Yang, Feng Wang, Ying Wang, Jintang Du, Lucy Lu, Yan Liu, Holly Parker
Rok vydání:	2016
Předmět:	Agonist 0301 basic medicine endocrine system medicine.drug_class Recombinant Fusion Proteins Mice Obese Peptide Peptide hormone 010402 general chemistry Immunoglobulin light chain Protein Engineering Glucagon 01 natural sciences Catalysis Antibodies Receptors Gastrointestinal Hormone Rats Sprague-Dawley Mice 03 medical and health sciences Gastric inhibitory polypeptide Glucagon-Like Peptide 1 medicine Animals Humans Receptor chemistry.chemical_classification Chemistry 010405 organic chemistry digestive oral and skin physiology Body Weight General Chemistry General Medicine Fusion protein Rats 0104 chemical sciences HEK293 Cells 030104 developmental biology Biochemistry Female Immunoglobulin Light Chains Immunoglobulin Heavy Chains Peptides hormones hormone substitutes and hormone antagonists Half-Life
Zdroj:	Angewandte Chemie. 128:12663-12666
ISSN:	0044-8249
DOI:	10.1002/ange.201606321
Popis:	Glucagon-like peptide-1 (GLP-1) receptor (GLP-1R), glucagon (GCG) receptor (GCGR), and glucose-dependent insulinotropic polypeptide (GIP, also known as gastric inhibitory polypeptide) receptor (GIPR), are three metabolically related peptide hormone receptors. A novel approach to the generation of multifunctional antibody agonists that activate these receptors has been developed. Native or engineered peptide agonists for GLP-1R, GCGR, and GIPR were fused to the N-terminus of the heavy chain or light chain of an antibody, either alone or in pairwise combinations. The fusion proteins have similar in vitro biological activities on the cognate receptors as the corresponding peptides, but circa 100-fold longer plasma half-lives. The GLP-1R mono agonist and GLP-1R/GCGR dual agonist antibodies both exhibit potent effects on glucose control and body weight reduction in mice, with the dual agonist antibody showing enhanced activity in the latter.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3d924f849ef9552ebde8c06a28da7b6c https://doi.org/10.1002/ange.201606321 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.