title: NMR structure of the glucose-dependent insulinotropic polypeptide fragment, GIP(1-30)amide.
abstract: Glucose-dependent insulinotropic polypeptide is an incretin hormone that stimulates insulin secretion and reduces postprandial glycaemic excursions. The glucose-dependent action of GIP on pancreatic beta-cells has attracted attention towards its exploitation as a potential drug for type 2 diabetes. Use of NMR or X-ray crystallography is vital to determine the three-dimensional structure of the peptide. Therefore, to understand the basic structural requirements for the biological activity of GIP, the solution structure of the major biologically active fragment, GIP(1-30)amide, was investigated by proton NMR spectroscopy and molecular modelling. The structure is characterised by a full length alpha-helical conformation between residues F(6) and A(28). This structural information could play an important role in the design of therapeutic agents based upon GIP receptor agonists.
authors.affiliation: Department of Biochemistry, Centre for Synthesis and Chemical Biology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Iñigo
authors.initials: I
authors.lastname: Alaña
authors.forename: Chandralal M
authors.initials: CM
authors.lastname: Hewage
authors.forename: J Paul G
authors.initials: JP
authors.lastname: Malthouse
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Parker
authors.forename: Victor A
authors.initials: VA
authors.lastname: Gault
authors.forename: Finbarr P M
authors.initials: FP
authors.lastname: O'Harte
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D005749:Gastric Inhibitory Polypeptide / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary
chemical_list: D010446:Peptide Fragments; D005749:Gastric Inhibitory Polypeptide