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NMR structure of the glucose-dependent insulinotropic polypeptide fragment, GIP(1-30)amide
Iñigo Alaña1, Chandralal M Hewage, J Paul G Malthouse
1Department of Biochemistry, Centre for Synthesis and Chemical Biology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
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.
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