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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.

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


Authors

Mengjie Liu

Simon J. Mountford

Rachel R. Richardson

Marleen Groenen

Philip E. Thompson



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 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.

Citation

Liu, M., Mountford, S. J., Richardson, R. R., Groenen, M., Holliday, N. D., & Thompson, P. E. (2016). Optically pure, structural and fluorescent analogues of a dimeric Y4 receptor agonist derived by an olefin metathesis approach. Journal of Medicinal Chemistry, 59(13), 6059-6069. https://doi.org/10.1021/acs.jmedchem.6b00310

Journal Article Type Article
Acceptance Date Jun 13, 2016
Online Publication Date Jun 28, 2016
Publication Date Jul 14, 2016
Deposit Date Jun 17, 2016
Publicly Available Date Jun 28, 2016
Journal Journal of Medicinal Chemistry
Print ISSN 0022-2623
Electronic ISSN 1520-4804
Publisher American Chemical Society
Peer Reviewed Peer Reviewed
Volume 59
Issue 13
Pages 6059-6069
DOI https://doi.org/10.1021/acs.jmedchem.6b00310
Public URL https://nottingham-repository.worktribe.com/output/795390
Publisher URL http://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.6b00310
Contract Date Jun 17, 2016

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