| Structural highlights
Publication Abstract from PubMed
Cyclic constraints are incorporated here 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 beta-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.
Short hydrophobic peptides with cyclic constraints are potent glucagon-like peptide-1 receptor (GLP-1R) agonists.,Hoang HN, Song K, Hill TA, Derksen DR, Edmonds DJ, Kok WM, Limberakis C, Liras S, Loria PM, Mascitti V, Mathiowetz AM, Mitchell JM, Piotrowski DW, Price DA, Stanton RV, Suen JY, Withka JM, Griffith DA, Fairlie DP J Med Chem. 2015 Apr 3. PMID:25839426[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hoang HN, Song K, Hill TA, Derksen DR, Edmonds DJ, Kok WM, Limberakis C, Liras S, Loria PM, Mascitti V, Mathiowetz AM, Mitchell JM, Piotrowski DW, Price DA, Stanton RV, Suen JY, Withka JM, Griffith DA, Fairlie DP. Short hydrophobic peptides with cyclic constraints are potent glucagon-like peptide-1 receptor (GLP-1R) agonists. J Med Chem. 2015 Apr 3. PMID:25839426 doi:http://dx.doi.org/10.1021/acs.jmedchem.5b00166
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