Quantitative MALDI-MS Binding Assays: An Alternative to Radiolabeling

ChemMedChem, 2016, Volume: 11, Issue: 23, Pages: 2582-2587, DOI: 10.1002/cmdc.201600447

M. Rossato,  G. Miralles, C. M’Kadmi, M. Maingot, M. Amblard, B. Mouillac, D. Gagne, J. Martinez, G. Subra, C. Enjalbal, S. Cantel, 


Radiolabeling of ligands is still the gold std. in the study of high-affinity receptor-ligand interactions. In an effort toward safer and simpler alternatives to the use of radioisotopes, we developed a quant. and highly sensitive matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) method that relies on the use of chem. tagged ligands designed to be specifically detectable when present as traces in complex biol. mixts. such as cellular lysates. This innovative technol. allows easy, sensitive detection and accurate quantification of analytes at the sub-nanomolar level. After statistical validation, we were able to perform pharmacol. evaluations of G protein-coupled receptor (V1A-R)-ligand interactions. Both satn. and competitive binding assays were successfully processed.