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.
Actions (Archive Staff Only)