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Fluorinated Carbohydrates as Lectin Ligands: Biorelevant Sensors with Capacity to Monitor Anomer Affinity in 19F-NMR-Based Inhibitor Screening
- Source :
- European Journal of Organic Chemistry, European Journal of Organic Chemistry; Vol 2012, Digital.CSIC. Repositorio Institucional del CSIC, instname
- Publication Year :
- 2012
- Publisher :
- Wiley, 2012.
-
Abstract
- 11 páginas, 4 figurasd, 2 esquemas -- PAGS nros. 4354-4364<br />Our 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 screening<br />This 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”)
- Subjects :
- Mannosides
Anomer
drug design
Stereochemistry
carbohydrates
Medicinal chemistry
Fluorine-19 NMR
010402 general chemistry
01 natural sciences
dendrimers
chemistry.chemical_compound
fluorine
Dendrimer
inhibitors
Molecule
Physical and Theoretical Chemistry
biology
010405 organic chemistry
Chemistry
Ligand
Organic Chemistry
Lectin
lectins
3. Good health
0104 chemical sciences
biology.protein
Derivative (chemistry)
Subjects
Details
- ISSN :
- 1434193X
- Volume :
- 2012
- Database :
- OpenAIRE
- Journal :
- European Journal of Organic Chemistry
- Accession number :
- edsair.doi.dedup.....5855adb31984437e8ec37686fbd0321e