Skip to main content

Research Repository

Advanced Search

Identification of a Cyanine-dye labeled peptidic ligand for Y₁R and Y₄R, based upon the Neuropeptide Y C-terminal analogue, BVD-15

Liu, Mengjie; Richardson, Rachel R.; Mountford, Simon J.; Zhang, Lei; Tempone, Matheus H.; Herzog, Herbert; Holliday, Nicholas D.; Thompson, Philip E.

Authors

Mengjie Liu

Rachel R. Richardson

Simon J. Mountford

Lei Zhang

Matheus H. Tempone

Herbert Herzog

Philip E. Thompson



Abstract

Traceable truncated Neuropeptide Y (NPY) analogues with Y₁ receptor (Y₁R) affinity and selectivity are highly desirable tools in studying receptor location, regulation, and biological functions. A range of fluorescently labeled analogues of a reported Y₁R/Y₄R preferring ligand BVD-15 have been prepared and evaluated using high content imaging techniques. One peptide, [Lys²(sCy5), Arg⁴]BVD-15, was characterized as an Y₁R antagonist with a pKD of 7.2 measured by saturation analysis using fluorescent imaging. The peptide showed 8-fold lower affinity for Y₄R (pKD = 6.2) and was a partial agonist at this receptor. The suitability of [Lys²(sCy5), Arg⁴]BVD-15 for Y₁R and Y₄R competition binding experiments was also demonstrated in intact cells. The nature of the label was shown to be critical with replacement of sCy5 by the more hydrophobic Cy5.5 resulting in a switch from Y₁R antagonist to Y₁R partial agonist.

Citation

Liu, M., Richardson, R. R., Mountford, S. J., Zhang, L., Tempone, M. H., Herzog, H., …Thompson, P. E. (2016). Identification of a Cyanine-dye labeled peptidic ligand for Y₁R and Y₄R, based upon the Neuropeptide Y C-terminal analogue, BVD-15. Bioconjugate Chemistry, 27(9), 2166-2175. https://doi.org/10.1021/acs.bioconjchem.6b00376

Journal Article Type Article
Acceptance Date Aug 8, 2016
Online Publication Date Aug 25, 2016
Publication Date Aug 11, 2016
Deposit Date Mar 23, 2017
Publicly Available Date Mar 28, 2024
Journal Bioconjugate Chemistry
Print ISSN 1043-1802
Electronic ISSN 1520-4812
Publisher American Chemical Society
Peer Reviewed Peer Reviewed
Volume 27
Issue 9
Pages 2166-2175
DOI https://doi.org/10.1021/acs.bioconjchem.6b00376
Keywords Neuropeptide Y, Fluorescent ligand, G protein coupled receptor, High content imaging
Public URL https://nottingham-repository.worktribe.com/output/805856
Publisher URL http://pubs.acs.org/doi/abs/10.1021/acs.bioconjchem.6b00376
Additional Information This document is the unedited author's version of a submitted work that was subsequently accepted for publication in the journal Bioconjugate Chemistry, Copyright © 2016 American Chemical Society after peer review. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/acs.bioconjchem.6b00376