Paper Citing NAMD - Abstract
Azcune, Itxaso; Balentova, Eva; Sagartzazu-Aizpurua, Maialen; Ignacio Santos, J.; Miranda, Jose I.; Fratila, Raluca M.; Aizpurua, Jesus M.
Modulating Lectin Inhibition with N-Glycosyl-1,2,3-triazole Scaffolds
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 12, 2434-2444, APR 2013
The synthesis of three families of sialyl LewisX (sLeX) mimetics based on triazole and bis-triazole scaffolds is reported. The flexibility of these mimetics is dictated by the scaffold and gradually increases from flexible to rigid. All three families were accessible by straightforward synthetic routes and by taking advantage of the unique features and high yields of CuI-catalyzed alkyneazide cycloaddition (CuAAC) reaction. Glycopeptidomimetics 1215 were submitted to an extensive evaluation of their binding affinities towards fucose-specific Ulex Europaeus lectin I by using conformational analysis (molecular dynamics), docking calculations, and saturation-transfer difference (STD) NMR experiments. The results reveal that the recognition of the ligands is mostly dictated by the fucose moiety and that semi-rigid ligands are better sLex mimic candidates because their degree of flexibility enables the modulation of their conformation to the best-fitting position.
