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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Journal of Medicinal Chemistry |
| Vol/bind | 59 |
| Udgave nummer | 10 |
| Sider (fra-til) | 4849-4858 |
| Antal sider | 10 |
| ISSN | 0022-2623 |
| DOI | |
| Status | Udgivet - 26 maj 2016 |
| Udgivet eksternt | Ja |
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