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The bioactive conformation of glucose-dependent insulinotropic polypeptide by NMR and CD spectroscopy

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

Alana, Inigo, Malthouse, J Paul G, O'Harte, Finbarr PM and Hewage, Chandralal M (2007) The bioactive conformation of glucose-dependent insulinotropic polypeptide by NMR and CD spectroscopy. PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 68 (1). pp. 92-99. [Journal article]

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DOI: 10.1002/prot.21372

Abstract

Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal incretin hormone, which modulates physiological insulin secretion. Because of its glucose-sensitive insulinotropic activity, there has been a considerable interest in utilizing the hormone as a potential treatment for type 2 diabetes. Structural parameters obtained from NMR spectroscopy combined with molecular modeling techniques play a vital role in the design of new therapeutic drugs. Therefore, to understand the structural requirements for the biological activity of GIP, the solution structure of GIP was investigated by circular dichroism (CD) followed by proton nuclear magnetic resonance (NMR) spectroscopy. CD studies showed an increase in the helical character of the peptide with increasing concentration of trifluoroethanol (TFE) up to 5%. Therefore, the solution structure of GIP in 50% TFE was determined. It was found that there was an a-helix between residues 6 and 29, which tends to extend further up to residue 36. The implications of the C-terminal extended helical segment in the inhibitory properties of GIP on gastric acid secretion are discussed. It is shown that the adoption by GIP of an a-helical secondary structure is a requirement for its biological activity. Knowledge of the solution structure of GIP will help in the understanding of how the peptide interacts with its receptor and aids in the design of new therapeutic agents useful for the treatment of diabetes.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
ID Code:6439
Deposited By:Professor Finbarr O'Harte
Deposited On:11 Jan 2010 10:35
Last Modified:27 Jun 2011 15:28

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