Development and Characterization of a Potent Free Fatty Acid Receptor 1 (FFA1) Fluorescent Tracer

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Development and Characterization of a Potent Free Fatty Acid Receptor 1 (FFA1) Fluorescent Tracer. / Christiansen, Elisabeth; Hudson, Brian D; Hansen, Anders Højgaard; Milligan, Graeme; Ulven, Trond.

In: Journal of Medicinal Chemistry, Vol. 59, No. 10, 2016, p. 4849-4858.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Christiansen, E, Hudson, BD, Hansen, AH, Milligan, G & Ulven, T 2016, 'Development and Characterization of a Potent Free Fatty Acid Receptor 1 (FFA1) Fluorescent Tracer', Journal of Medicinal Chemistry, vol. 59, no. 10, pp. 4849-4858. https://doi.org/10.1021/acs.jmedchem.6b00202

APA

Christiansen, E., Hudson, B. D., Hansen, A. H., Milligan, G., & Ulven, T. (2016). Development and Characterization of a Potent Free Fatty Acid Receptor 1 (FFA1) Fluorescent Tracer. Journal of Medicinal Chemistry, 59(10), 4849-4858. https://doi.org/10.1021/acs.jmedchem.6b00202

Vancouver

Christiansen E, Hudson BD, Hansen AH, Milligan G, Ulven T. Development and Characterization of a Potent Free Fatty Acid Receptor 1 (FFA1) Fluorescent Tracer. Journal of Medicinal Chemistry. 2016;59(10):4849-4858. https://doi.org/10.1021/acs.jmedchem.6b00202

Author

Christiansen, Elisabeth ; Hudson, Brian D ; Hansen, Anders Højgaard ; Milligan, Graeme ; Ulven, Trond. / Development and Characterization of a Potent Free Fatty Acid Receptor 1 (FFA1) Fluorescent Tracer. In: Journal of Medicinal Chemistry. 2016 ; Vol. 59, No. 10. pp. 4849-4858.

Bibtex

@article{63d3e7d37c3e4e11ac2cce3c5b0afd22,
title = "Development and Characterization of a Potent Free Fatty Acid Receptor 1 (FFA1) Fluorescent Tracer",
abstract = "The free fatty acid receptor 1 (FFA1/GPR40) is a potential target for treatment of type 2 diabetes. Although several potent agonists have been described, there remains a strong need for suitable tracers to interrogate ligand binding to this receptor. We address this by exploring fluorophore-tethering to known potent FFA1 agonists. This led to the development of 4, a high affinity FFA1 tracer with favorable and polarity-dependent fluorescent properties. A close to ideal overlap between the emission spectrum of the NanoLuciferase receptor tag and the excitation spectrum of 4 enabled the establishment of a homogeneous BRET-based binding assay suitable for both detailed kinetic studies and high throughput competition binding studies. Using 4 as a tracer demonstrated that the compound acts fully competitively with selected synthetic agonists but not with lauric acid and allowed for the characterization of binding affinities of a diverse selection of known FFA1 agonists, indicating that 4 will be a valuable tool for future studies at FFA1.",
author = "Elisabeth Christiansen and Hudson, {Brian D} and Hansen, {Anders H{\o}jgaard} and Graeme Milligan and Trond Ulven",
year = "2016",
doi = "10.1021/acs.jmedchem.6b00202",
language = "English",
volume = "59",
pages = "4849--4858",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "10",

}

RIS

TY - JOUR

T1 - Development and Characterization of a Potent Free Fatty Acid Receptor 1 (FFA1) Fluorescent Tracer

AU - Christiansen, Elisabeth

AU - Hudson, Brian D

AU - Hansen, Anders Højgaard

AU - Milligan, Graeme

AU - Ulven, Trond

PY - 2016

Y1 - 2016

N2 - The free fatty acid receptor 1 (FFA1/GPR40) is a potential target for treatment of type 2 diabetes. Although several potent agonists have been described, there remains a strong need for suitable tracers to interrogate ligand binding to this receptor. We address this by exploring fluorophore-tethering to known potent FFA1 agonists. This led to the development of 4, a high affinity FFA1 tracer with favorable and polarity-dependent fluorescent properties. A close to ideal overlap between the emission spectrum of the NanoLuciferase receptor tag and the excitation spectrum of 4 enabled the establishment of a homogeneous BRET-based binding assay suitable for both detailed kinetic studies and high throughput competition binding studies. Using 4 as a tracer demonstrated that the compound acts fully competitively with selected synthetic agonists but not with lauric acid and allowed for the characterization of binding affinities of a diverse selection of known FFA1 agonists, indicating that 4 will be a valuable tool for future studies at FFA1.

AB - The free fatty acid receptor 1 (FFA1/GPR40) is a potential target for treatment of type 2 diabetes. Although several potent agonists have been described, there remains a strong need for suitable tracers to interrogate ligand binding to this receptor. We address this by exploring fluorophore-tethering to known potent FFA1 agonists. This led to the development of 4, a high affinity FFA1 tracer with favorable and polarity-dependent fluorescent properties. A close to ideal overlap between the emission spectrum of the NanoLuciferase receptor tag and the excitation spectrum of 4 enabled the establishment of a homogeneous BRET-based binding assay suitable for both detailed kinetic studies and high throughput competition binding studies. Using 4 as a tracer demonstrated that the compound acts fully competitively with selected synthetic agonists but not with lauric acid and allowed for the characterization of binding affinities of a diverse selection of known FFA1 agonists, indicating that 4 will be a valuable tool for future studies at FFA1.

U2 - 10.1021/acs.jmedchem.6b00202

DO - 10.1021/acs.jmedchem.6b00202

M3 - Journal article

VL - 59

SP - 4849

EP - 4858

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 10

ER -

ID: 189162335