Optically pure, structural and fluorescent analogues of a dimeric Y4 receptor agonist derived by an olefin metathesis approach
Liu, Mengjie and Mountford, Simon J and Richardson, Rachel R and Groenen, Marleen and Holliday, Nicholas D and Thompson, Philip E (2016) Optically pure, structural and fluorescent analogues of a dimeric Y4 receptor agonist derived by an olefin metathesis approach. Journal of Medicinal Chemistry . ISSN 1520-4804
Official URL: http://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.6b00310
The dimeric peptide 1 (BVD-74D, as a diastereomeric mixture) is a potent and selective Neuropeptide Y Y4 receptor agonist. It represents a valuable candidate in developing traceable ligands for pharmacological studies of Y4 receptors, and as a lead compound for anti-obesity drugs. Its optically pure stereoisomers along with analogues and fluorescently labelled variants were prepared by exploiting alkene metathesis reactions. The (2R,7R)- diaminosuberoyl containing peptide, (R,R)-1 had markedly higher affinity and agonist efficacy than its (S,S)-counterpart. Furthermore the sulfo-Cy5 labelled (R,R)-14 retained high agonist potency as a novel fluorescent ligand for imaging Y4 receptors.
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