title: Biological activity and three-dimensional structure of an agonist analog of bombesin.
abstract: JMV635, a nonapeptide analog of the active terminal nonapeptide segment of bombesin, was tested for its ability to stimulate in vitro amylase release from rat pancreatic acinar cells and to inhibit the binding of gastrin-releasing peptide to rat pancreatic acini. It was found to be a full agonist of bombesin and to recognize the bombesin receptor with moderate potency. The NMR proton assignments of JMV635 were achieved, and the conformations of JMV635 in aqueous solution and in trifluoroethanol at 297 K were determined using two-dimensional COSY, HOHAHA, NOESY and ROESY experiments. In trifluoroethanol, JMV635, like the active part of bombesin, showed a partial alpha-helical structure. These results were confirmed by circular dichroism and refined by restrained molecular dynamic methods. Structure calculations, using the distance and angle restraints obtained from NMR data on JMV635, gave a total of 75 structures which could be aligned to a root mean square deviation of the bond length of 0.007 A and of the valence angle of 1.55 degrees for the backbone atoms of the amino acid residues. The conformation is a well-defined right-handed alpha-helix in the C-terminal Q2-G6 segment and is less structured in the three C-terminal residues.
authors.affiliation: Institut Fédératif de Recherche Multidisciplinaire sur les Peptides, UPRESA CNRS 6014, UFR des Sciences, Université de Rouen, Mont-Saint-Aignan, France.
authors.forename: E
authors.initials: E
authors.lastname: Condamine
authors.forename: G
authors.initials: G
authors.lastname: Chapdeleine
authors.forename: L
authors.initials: L
authors.lastname: Demarcy
authors.forename: J F
authors.initials: JF
authors.lastname: Duclos
authors.forename: D
authors.initials: D
authors.lastname: Davoust
authors.forename: M
authors.initials: M
authors.lastname: Llinares
authors.forename: J
authors.initials: J
authors.lastname: Azay
authors.forename: J
authors.initials: J
authors.lastname: Martinez
authors.forename: S
authors.initials: S
authors.lastname: Chapelle
mesh_terms: D000681:Amylases / Q000378:metabolism; D000818:Animals; D001839:Bombesin / Q000819:agonists / Q000031:analogs & derivatives*; D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009842:Oligopeptides; D000681:Amylases; D001839:Bombesin