Short hydrophobic peptides with cyclic constraints are potent glucagon-like peptide-1 receptor (GLP-1R) agonists

Hoang, Huy N., Song, Kun, Hill, Timothy A., Derksen, David R., Edmonds, David J., Kok, W. Mei, Limberakis, Chris, Liras, Spiros, Loria, Paula M., Mascitti, Vincent, Mathiowetz, Alan M., Mitchell, Justin M., Piotrowski, David W., Price, David A., Stanton, Robert V., Suen, Jacky Y., Withka, Jane M., Griffith, David A. and Fairlie, David P. (2015) Short hydrophobic peptides with cyclic constraints are potent glucagon-like peptide-1 receptor (GLP-1R) agonists. Journal of Medicinal Chemistry, 58 9: 4080-4085. doi:10.1021/acs.jmedchem.5b00166

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Author Hoang, Huy N.
Song, Kun
Hill, Timothy A.
Derksen, David R.
Edmonds, David J.
Kok, W. Mei
Limberakis, Chris
Liras, Spiros
Loria, Paula M.
Mascitti, Vincent
Mathiowetz, Alan M.
Mitchell, Justin M.
Piotrowski, David W.
Price, David A.
Stanton, Robert V.
Suen, Jacky Y.
Withka, Jane M.
Griffith, David A.
Fairlie, David P.
Title Short hydrophobic peptides with cyclic constraints are potent glucagon-like peptide-1 receptor (GLP-1R) agonists
Journal name Journal of Medicinal Chemistry   Check publisher's open access policy
ISSN 0022-2623
1520-4804
Publication date 2015-04-03
Year available 2015
Sub-type Article (original research)
DOI 10.1021/acs.jmedchem.5b00166
Open Access Status File (Author Post-print)
Volume 58
Issue 9
Start page 4080
End page 4085
Total pages 6
Place of publication Washington, DC, United States
Publisher American Chemical Society
Language eng
Abstract Cyclic constraints are incorporated into an 11-residue analogue of the N-terminus of glucagon-like peptide-1 (GLP-1) to investigate effects of structure on agonist activity. Cyclization through linking side chains of residues 2 and 5 or 5 and 9 produced agonists at nM concentrations in a cAMP assay. 2D NMR and CD spectra revealed an N-terminal β-turn and a C-terminal helix that differentially influenced affinity and agonist potency. These structures can inform development of small molecule agonists of the GLP-1 receptor to treat type 2 diabetes.
Keyword Agonist potency
Drug design
Circular dichroism
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 1027369
LP110200213
CE140100011
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Institute for Molecular Bioscience - Publications
 
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Created: Tue, 14 Apr 2015, 19:49:24 EST by Susan Allen on behalf of Institute for Molecular Bioscience