Abstract
| Language | English |
|---|---|
| Pages | 882-888 |
| Journal | Biochim Biophys Acta. |
| Volume | 1814 |
| Issue number | 7 |
| Publication status | Published - 1 Jul 2011 |
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Conformational, receptor interaction and alanine scan studies of glucose-dependent insulinotropic polypeptide. / Venneti, KC; Malthouse, JP; O'Harte, Finbarr; Hewage, CM.
In: Biochim Biophys Acta., Vol. 1814, No. 7, 01.07.2011, p. 882-888.Research output: Contribution to journal › Article
TY - JOUR
T1 - Conformational, receptor interaction and alanine scan studies of glucose-dependent insulinotropic polypeptide.
AU - Venneti, KC
AU - Malthouse, JP
AU - O'Harte, Finbarr
AU - Hewage, CM
PY - 2011/7/1
Y1 - 2011/7/1
N2 - Glucose-dependent insulinotropic polypeptide (GIP) is an insulinotropic incretin hormone that stimulates insulin secretion during a meal. GIP has glucose lowering abilities and hence is considered as a potential target molecule for type 2 diabetes therapy. In this article, we present the solution structure of GIP in membrane-mimicking environments by proton NMR spectroscopy and molecular modelling. GIP adopts an α-helical conformation between residues Phe(6)-Gly(31) and Ala(13)-Gln(29) for micellar and bicellar media, respectively. Previously we examined the effect of N-terminal Ala substitution in GIP, but here eight GIP analogues were synthesised by replacing individual residues within the central 8-18 region with alanine. These studies showed relatively minor changes in biological activity as assessed by insulin releasing potency. However, at higher concentration, GIP(Ala(16)), and GIP(Ala(18)) showed insulin secreting activity higher than the native GIP (P
AB - Glucose-dependent insulinotropic polypeptide (GIP) is an insulinotropic incretin hormone that stimulates insulin secretion during a meal. GIP has glucose lowering abilities and hence is considered as a potential target molecule for type 2 diabetes therapy. In this article, we present the solution structure of GIP in membrane-mimicking environments by proton NMR spectroscopy and molecular modelling. GIP adopts an α-helical conformation between residues Phe(6)-Gly(31) and Ala(13)-Gln(29) for micellar and bicellar media, respectively. Previously we examined the effect of N-terminal Ala substitution in GIP, but here eight GIP analogues were synthesised by replacing individual residues within the central 8-18 region with alanine. These studies showed relatively minor changes in biological activity as assessed by insulin releasing potency. However, at higher concentration, GIP(Ala(16)), and GIP(Ala(18)) showed insulin secreting activity higher than the native GIP (P
M3 - Article
VL - 1814
SP - 882
EP - 888
JO - BBA - General Subjects
T2 - BBA - General Subjects
JF - BBA - General Subjects
SN - 0304-4165
IS - 7
ER -