Towards sugar derivatives as toxin-blocking pharmaceuticals: STD NMR spectroscopy as versatile tool for affinity assessment in drug development

A protocol based on saturation transfer difference (STD)-NMR spectroscopy competition experiments is presented as a fast compound-screening method (30 min acquisition time per compound) capable of evaluating ligand properties for the lectin site with the intention of selecting compounds for iterative refinement. Glycosides with variations in the aglycon and plant toxin viscumin (VAA) were studied systematically. The best hits were further analyzed via docking simulations to rationalize an increased affinity structurally. The strategy described can readily be extended to other medically relevant lectins.