Poster Presentation 12th Australian Peptide Conference 2017

Why are dimers of the NPY C-terminus superpotent, selective Y receptor ligands? (#128)

Philip Thompson 1 , Mengjie Liu 1 , Simon J Mountford 1 , Rachel R Richardson 1 2 , Nicholas D Holliday 2
  1. Medicinal Chemistry, MIPS, Monash University, Parkville, VIC, Australia
  2. Cell Signalling Research Group, School of Life Sciences, , University of Nottingham, Nottingham, UK

A series of C-terminal peptide dimers related to neuropeptide Y have been f​ound to be high affinity and selective ligands for Y receptors. ​The dimers have non-native connectivity and are challenging for synthesis hindering SAR studies, but we have ​developed useful methods including the development of heterodimeric peptides and fluorescent ligands.​ We are studying the mechanism by which such ligands have such high affinity, which remain unclear but clearly have implications for understanding GPCR pharmacology more generally.

  1. Liu, M.; Mountford, S. J.; Richardson, R. R.; Groenen, M.; Holliday, N. D.; Thompson, P. E. Optically Pure, Structural, and Fluorescent Analogues of a Dimeric Y4 Receptor Agonist Derived by an Olefin Metathesis Approach. J. Med. Chem. 2016, 59, 6059-6069.