Optically Pure, Structural, and Fluorescent Analogues of a Dimeric Y4 Receptor Agonist Derived by an Olefin Metathesis Approach

详细信息    查看全文

• 作者：Mengjie Liu ; Simon J. Mountford ; Rachel R. Richardson ; Marleen Groenen ; Nicholas D. Holliday ; Philip E. Thompson
• 刊名：Journal of Medicinal Chemistry
• 出版年：2016
• 出版时间：July 14, 2016
• 年：2016
• 卷：59
• 期：13
• 页码：6059-6069
• 全文大小：661K
• 年卷期：0
• ISSN：1520-4804

文摘

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.