| Literature DB >> 25839426 |
Huy N Hoang1, Kun Song, Timothy A Hill1, David R Derksen, David J Edmonds, W Mei Kok1, Chris Limberakis, Spiros Liras, Paula M Loria, Vincent Mascitti, Alan M Mathiowetz, Justin M Mitchell1, David W Piotrowski, David A Price, Robert V Stanton, Jacky Y Suen1, Jane M Withka, David A Griffith, David P Fairlie1.
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.Entities:
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Year: 2015 PMID： 25839426 DOI： 10.1021/acs.jmedchem.5b00166
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446