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

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...

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Main Authors: Liu, Mengjie, Mountford, Simon J., Richardson, Rachel R., Groenen, Marleen, Holliday, Nicholas D., Thompson, Philip E.
Format: Article
Published: American Chemical Society 2016
Online Access:https://eprints.nottingham.ac.uk/34144/
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author Liu, Mengjie
Mountford, Simon J.
Richardson, Rachel R.
Groenen, Marleen
Holliday, Nicholas D.
Thompson, Philip E.
author_facet Liu, Mengjie
Mountford, Simon J.
Richardson, Rachel R.
Groenen, Marleen
Holliday, Nicholas D.
Thompson, Philip E.
author_sort Liu, Mengjie
building Nottingham Research Data Repository
collection Online Access
description 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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spelling nottingham-341442020-05-04T17:56:49Z https://eprints.nottingham.ac.uk/34144/ Optically pure, structural and fluorescent analogues of a dimeric Y4 receptor agonist derived by an olefin metathesis approach Liu, Mengjie Mountford, Simon J. Richardson, Rachel R. Groenen, Marleen Holliday, Nicholas D. Thompson, Philip E. 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. American Chemical Society 2016-06-13 Article PeerReviewed Liu, Mengjie, Mountford, Simon J., Richardson, Rachel R., Groenen, Marleen, 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 http://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.6b00310 doi:10.1021/acs.jmedchem.6b00310 doi:10.1021/acs.jmedchem.6b00310
spellingShingle Liu, Mengjie
Mountford, Simon J.
Richardson, Rachel R.
Groenen, Marleen
Holliday, Nicholas D.
Thompson, Philip E.
Optically pure, structural and fluorescent analogues of a dimeric Y4 receptor agonist derived by an olefin metathesis approach
title Optically pure, structural and fluorescent analogues of a dimeric Y4 receptor agonist derived by an olefin metathesis approach
title_full Optically pure, structural and fluorescent analogues of a dimeric Y4 receptor agonist derived by an olefin metathesis approach
title_fullStr Optically pure, structural and fluorescent analogues of a dimeric Y4 receptor agonist derived by an olefin metathesis approach
title_full_unstemmed Optically pure, structural and fluorescent analogues of a dimeric Y4 receptor agonist derived by an olefin metathesis approach
title_short Optically pure, structural and fluorescent analogues of a dimeric Y4 receptor agonist derived by an olefin metathesis approach
title_sort optically pure, structural and fluorescent analogues of a dimeric y4 receptor agonist derived by an olefin metathesis approach
url https://eprints.nottingham.ac.uk/34144/
https://eprints.nottingham.ac.uk/34144/
https://eprints.nottingham.ac.uk/34144/