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Lectin‐Based Drug Design: Combined Strategy to Identify Lead Compounds using STD NMR Spectroscopy, Solid‐Phase Assays and Cell Binding for a Plant Toxin Model
Author(s) -
Ribeiro João P.,
André Sabine,
Cañada F. Javier,
Gabius HansJoachim,
Butera Anna Paola,
Alves Ricardo José,
JiménezBarbero Jesús
Publication year - 2010
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200900476
Subject(s) - glycan , chemistry , lectin , biochemistry , nuclear magnetic resonance spectroscopy , lead compound , stereochemistry , combinatorial chemistry , glycoprotein , in vitro
The growing awareness of the sugar code—i.e. the biological functionality of glycans—is leading to increased interest in lectins as drug targets. The aim of this study was to establish a strategic combination of screening procedures with increased biorelevance. As a model, we used a potent plant toxin (viscumin) and lactosides synthetically modified at the C6/C6′ positions and the reducing end aglycan. Changes in the saturation transfer difference (STD) in NMR spectroscopy, applied in inhibition assays, yielded evidence for ligand activity and affinity differences. Inhibitory potency was confirmed by the blocking of lectin binding to a glycoprotein‐bearing matrix. In cell‐based assays, iodo/azido‐substituted lactose derivatives were comparatively active. Interestingly, cell‐type dependence was observed, indicating the potential of synthetic carbohydrate derivative to interact with lectins in a cell‐type (glycan profile)‐specific manner. These results are relevent to research into human lectins, glycosciences, and beyond.