Identification of a cyanine-dye labeled peptidic ligand for Y1R and Y4R, based upon the neuropeptide y C-terminal analogue, BVD-15

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

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)2166-2175
Number of pages10
JournalBioconjugate Chemistry
Volume27
Issue number9
DOIs
Publication statusPublished - 21 Sep 2016

Cite this

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. In: Bioconjugate Chemistry. 2016 ; Vol. 27, No. 9. pp. 2166-2175.
@article{90198ff86f904088b8cefaa9af6585de,
title = "Identification of a cyanine-dye labeled peptidic ligand for Y1R and Y4R, based upon the neuropeptide y C-terminal analogue, BVD-15",
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.",
author = "Mengjie Liu and Richardson, {Rachel R.} and Mountford, {Simon J.} and Lei Zhang and Tempone, {Matheus H.} and Herbert Herzog and Holliday, {Nicholas D.} and Thompson, {Philip E.}",
year = "2016",
month = "9",
day = "21",
doi = "10.1021/acs.bioconjchem.6b00376",
language = "English",
volume = "27",
pages = "2166--2175",
journal = "Bioconjugate Chemistry",
issn = "1043-1802",
publisher = "American Chemical Society",
number = "9",

}

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.

In: Bioconjugate Chemistry, Vol. 27, No. 9, 21.09.2016, p. 2166-2175.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Identification of a cyanine-dye labeled peptidic ligand for Y1R and Y4R, based upon the neuropeptide y C-terminal analogue, BVD-15

AU - Liu, Mengjie

AU - Richardson, Rachel R.

AU - Mountford, Simon J.

AU - Zhang, Lei

AU - Tempone, Matheus H.

AU - Herzog, Herbert

AU - Holliday, Nicholas D.

AU - Thompson, Philip E.

PY - 2016/9/21

Y1 - 2016/9/21

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84988521757&partnerID=8YFLogxK

U2 - 10.1021/acs.bioconjchem.6b00376

DO - 10.1021/acs.bioconjchem.6b00376

M3 - Article

VL - 27

SP - 2166

EP - 2175

JO - Bioconjugate Chemistry

JF - Bioconjugate Chemistry

SN - 1043-1802

IS - 9

ER -