PMID: 11311060Apr 20, 2001Paper

Development of potent truncated glucagon antagonists

Journal of Medicinal Chemistry
J M AhnV J Hruby

Abstract

In pursuit of truncated glucagon analogues that can interact with the glucagon receptor with substantial binding affinity, 23 truncated glucagon analogues have been designed and synthesized. These truncated analogues consist of several fragments of glucagon with 11 or 12 amino acid residues (1-4), conformationally constrained analogues containing the sequence of the middle region of glucagon (5-15), and truncated analogues containing the sequence of the C-terminal region (16-23). Biological assays of these analogues showed that the truncated glucagon analogues with the sequence of the C-terminal region possess significantly better binding affinity compared to the truncated analogues with the sequence of the middle region, and these analogues (17-23) demonstrated potent antagonistic activity (pA(2) values between 6.5 and 7.5). On the basis of these results, it can be suggested that glucagon interacts with its receptor with two hydrophobic patches located in the middle and the C-terminal regions of glucagon, and both hydrophobic patches are necessary for significant receptor recognition. These two hydrophobic binding motifs, located in two different regions of glucagon, appear to be the reason why the earlier attempts to obtain t...Continue Reading

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Citations

Sep 11, 2001·Bioorganic & Medicinal Chemistry Letters·L L ChangW K Hagmann
Jul 19, 2013·Nature·Fai Yiu SiuRaymond C Stevens
Dec 24, 2013·Trends in Pharmacological Sciences·Kaspar HollensteinRaymond C Stevens
Jun 14, 2005·Expert Opinion on Therapeutic Targets·Kyle W SloopJulie S Moyers
Aug 1, 2015·Nature Communications·Linlin YangHualiang Jiang
May 6, 2011·British Journal of Pharmacology·Laurence J MillerKaleeckal G Harikumar
Jan 13, 2018·Journal of Peptide Science : an Official Publication of the European Peptide Society·Richard D DiMarchiMatthias Tschöp
Sep 5, 2001·The Journal of Peptide Research : Official Journal of the American Peptide Society·J M AhnV J Hruby
Nov 28, 2019·Journal of Medicinal Chemistry·Joseph ChabenneRichard D DiMarchi
Apr 7, 2021·Journal of Medicinal Chemistry·Bin YangRichard D DiMarchi

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