title: Structural requirements of the N-terminal region of GLP-1-[7-37]-NH2 for receptor interaction and cAMP production.
abstract: A series of GLP-1-[7-36]-NH(2) (tGLP-1) and GLP-1-[7-37] analogs modified in position 7, 8, 9 and 36, have been designed and evaluated on murine GLP-1 receptors expressed in RIN T3 cells for both their affinity and activity. Ten of the synthesized peptides were found full agonists with activities superior or at least equal to that of the native hormone. Five of them were investigated for their plasmatic stability and the most stable, [a(8)-desR(36)]GLP-1-[7-37]- NH(2) (Compound 8), evaluated in vivo in a glucose tolerance test which confirmed a clearly longer activity than that of the native hormone. We also performed circular dichroism study and propose a hypothetical structural model explaining the most part of observed activities of GLP-1 analogs on RIN T3 cells.
authors.affiliation: Centre de Biochimie Structurale, CNRS UMR 5048 - UM1 - INSERM UMR 554, 29 rue de Navacelles, 34090 Montpellier Cedex, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Sarrauste de Menthière
authors.forename: Alain
authors.initials: A
authors.lastname: Chavanieu
authors.forename: Gérard
authors.initials: G
authors.lastname: Grassy
authors.forename: Stéphane
authors.initials: S
authors.lastname: Dalle
authors.forename: Guillermo
authors.initials: G
authors.lastname: Salazar
authors.forename: Alain
authors.initials: A
authors.lastname: Kervran
authors.forename: Bruno
authors.initials: B
authors.lastname: Pfeiffer
authors.forename: Pierre
authors.initials: P
authors.lastname: Renard
authors.forename: Philippe
authors.initials: P
authors.lastname: Delagrange
authors.forename: Dominique
authors.initials: D
authors.lastname: Manechez
authors.forename: David
authors.initials: D
authors.lastname: Bakes
authors.forename: Alain
authors.initials: A
authors.lastname: Ktorza
authors.forename: Bernard
authors.initials: B
authors.lastname: Calas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002942:Circular Dichroism; D000242:Cyclic AMP / Q000096:biosynthesis* / Q000737:chemistry; D005768:Gastrointestinal Hormones / Q000138:chemical synthesis* / Q000378:metabolism; D005934:Glucagon / Q000138:chemical synthesis* / Q000378:metabolism; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D005951:Glucose Tolerance Test; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism; D011487:Protein Conformation; D011498:Protein Precursors / Q000138:chemical synthesis* / Q000378:metabolism; D051381:Rats; D018027:Receptors, Glucagon / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D005768:Gastrointestinal Hormones; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000242:Cyclic AMP