Fluorinated Carbohydrates as Lectin Ligands: Biorelevant Sensors with Capacity to Monitor Anomer Affinity in 19 F‐NMR‐Based Inhibitor Screening

• Published in: European journal of organic chemistry 2012-08, Vol.2012 (23), p.4354-4364
• Main Authors: André, Sabine, Cañada, F. Javier, Shiao, Tze Chieh, Largartera, Laura, Diercks, Tammo, Bergeron‐Brlek, Milan, el Biari, Khouzaima, Papadopoulos, Alex, Ribeiro, Joao P., Touaibia, Mohamed, Solís, Dolores, Menéndez, Margarita, Jiménez‐Barbero, Jesús, Roy, René, Gabius, Hans‐Joachim
• Format: Article
• Language: English
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201200397

Our recent description of pulse sequences for the intramolecular relay of 1 H polarization to the 19 F 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 19 F‐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 19 F 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 19 F 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 19 F‐NMR‐based inhibitor screening.