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

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 prepa...

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Main Authors: Liu, Mengjie, Richardson, Rachel R., Mountford, Simon J., Zhang, Lei, Tempone, Matheus H., Herzog, Herbert, Holliday, Nicholas D., Thompson, Philip E.
Format: Article
Published: American Chemical Society 2016
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Online Access:https://eprints.nottingham.ac.uk/41450/
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author Liu, Mengjie
Richardson, Rachel R.
Mountford, Simon J.
Zhang, Lei
Tempone, Matheus H.
Herzog, Herbert
Holliday, Nicholas D.
Thompson, Philip E.
author_facet Liu, Mengjie
Richardson, Rachel R.
Mountford, Simon J.
Zhang, Lei
Tempone, Matheus H.
Herzog, Herbert
Holliday, Nicholas D.
Thompson, Philip E.
author_sort Liu, Mengjie
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-414502020-05-04T18:07:14Z https://eprints.nottingham.ac.uk/41450/ 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. 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. American Chemical Society 2016-08-11 Article PeerReviewed Liu, Mengjie, Richardson, Rachel R., Mountford, Simon J., Zhang, Lei, Tempone, Matheus H., Herzog, Herbert, Holliday, Nicholas D. and Thompson, Philip 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). pp. 2166-2175. ISSN 1520-4812 Neuropeptide Y Fluorescent ligand G protein coupled receptor High content imaging http://pubs.acs.org/doi/abs/10.1021/acs.bioconjchem.6b00376 doi:10.1021/acs.bioconjchem.6b00376 doi:10.1021/acs.bioconjchem.6b00376
spellingShingle Neuropeptide Y
Fluorescent ligand
G protein coupled receptor
High content imaging
Liu, Mengjie
Richardson, Rachel R.
Mountford, Simon J.
Zhang, Lei
Tempone, Matheus H.
Herzog, Herbert
Holliday, Nicholas D.
Thompson, Philip E.
Identification of a Cyanine-dye labeled peptidic ligand for Y₁R and Y₄R, based upon the Neuropeptide Y C-terminal analogue, BVD-15
title Identification of a Cyanine-dye labeled peptidic ligand for Y₁R and Y₄R, based upon the Neuropeptide Y C-terminal analogue, BVD-15
title_full Identification of a Cyanine-dye labeled peptidic ligand for Y₁R and Y₄R, based upon the Neuropeptide Y C-terminal analogue, BVD-15
title_fullStr Identification of a Cyanine-dye labeled peptidic ligand for Y₁R and Y₄R, based upon the Neuropeptide Y C-terminal analogue, BVD-15
title_full_unstemmed Identification of a Cyanine-dye labeled peptidic ligand for Y₁R and Y₄R, based upon the Neuropeptide Y C-terminal analogue, BVD-15
title_short Identification of a Cyanine-dye labeled peptidic ligand for Y₁R and Y₄R, based upon the Neuropeptide Y C-terminal analogue, BVD-15
title_sort identification of a cyanine-dye labeled peptidic ligand for y₁r and y₄r, based upon the neuropeptide y c-terminal analogue, bvd-15
topic Neuropeptide Y
Fluorescent ligand
G protein coupled receptor
High content imaging
url https://eprints.nottingham.ac.uk/41450/
https://eprints.nottingham.ac.uk/41450/
https://eprints.nottingham.ac.uk/41450/