Optically pure, structural, and fluorescent analogues of a dimeric Y4 receptor agonist derived by an olefin metathesis approach

Mengjie Liu, Simon J. Mountford, Rachel R. Richardson, Marleen Groenen, Nicholas D. Holliday, Philip E. Thompson

Research output: Contribution to journalArticleResearchpeer-review

10 Citations (Scopus)

Abstract

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 antiobesity drugs. Its optically pure stereoisomers along with analogues and fluorescently labeled 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 labeled (R,R)-14 retained high agonist potency as a novel fluorescent ligand for imaging Y4 receptors.

Original languageEnglish
Pages (from-to)6059-6069
Number of pages11
JournalJournal of Medicinal Chemistry
Volume59
Issue number13
DOIs
Publication statusPublished - 14 Jul 2016

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