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SEC–MS as an Approach to Isolate and Directly Identifying Small Molecular GPCR–Ligands from Complex Mixtures Without Labeling |
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| Authors: | R J E Derks T Letzel C F de Jong A van Marle H Lingeman R Leurs H Irth |
| Institution: | 1. Leiden/Amsterdam Center for Drug Research (LACDR), Analytical Chemistry and Applied Spectroscopy, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands 4. Biomolecular Mass Spectrometry Unit, Department of Parasitology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands 3. Department of Basic Life Sciences, Technische Universit?t München, Weihenstephaner Berg 3, Freising, Weihenstephan, 85354, Germany 2. Leiden/Amsterdam Center for Drug Research (LACDR), Division of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands |
| Abstract: | G protein coupled receptors (GPCRs) belong to the most successful targets in drug discovery. However, the development of assays with an appropriately labeled high affinity reporter compound is laborious. In the present study an MS-based binding assay is described using the rat histamine receptor 2 (rH2) as a model GPCR system. Instead of using a purified receptor it is demonstrated that it is possible to use an unpurified receptor to extract active compounds from a solution or small mixture of compounds. By using SEC it is possible to separate the bound ligand from the unbound ligand. The major advantage of this approach is that there is no labeling of ligands required (direct monitoring based on the appropriate m/z values). |
| Keywords: | Column liquid chromatography Size-exclusion chromatography– MS GPCR– ligands Receptor binding Histamine receptor 2 |
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