11 páginas, 4 figurasd, 2 esquemas -- PAGS nros. 4354-4364Our recent description of pulse sequences for the intramolecular relay of 1H polarization to the 19F reporter of a carbohydrate ligand after saturation transfer from a cognate lectin prompted us to test the applicability of this technique for inhibitor screening. By strategically combining synthetic organic chemistry and cell assays with 19F-NMR-based competition experiments, we document the validity of this approach. Two mannose-specific leguminous agglutinins as receptors, the α-methyl derivative of 2-deoxy-2-fluoro-D-mannopyranoside as sensor and synthetic mannosides selected to represent different inhibitory capacities were used to establish a test panel. Signal amplitudes were found to vary among the two related lectins, and their precipitation by glycodendrimers enabled inherent limits to be set. The obtained experimental basis was then broadened by assaying a galactopyranoside-binding plant toxin, using 6-deoxy-6-fluoro-D-galactopyranose as a sensor molecule. The easy identification of the two anomeric signals by 19F NMR spectroscopy enabled ready detection of the preference of this lectin for the α-anomer and allowed the two individual inhibition profiles to be deduced. These 19F NMR spectroscopic data were in accord with the activities of inhibitors used to protect cells from toxicity. Our results therefore provide an experimental basis for 19F-NMR-based inhibitor screeningThis work was generously supported by the European Community (Marie Curie Research training grant MCRTN-CT-2005–19561), the Ministerio de Ciencia e Innovación (MICINN) (grant numbers CTQ2009-08536 and BFU2009-10052), and the Spanish Institute of Health Carlos III (ISCIII), under the initiative CIBER of Respiratory Diseases (CIBERES). The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement number 260600 (“GlycoHIT”)Peer reviewe
