Thio- and selenoglycosides as ligands for biomedically relevant lectins: Valency-activity correlations for benzene-based dithiogalactoside clusters and first assessment for (di)selenodigalactosides

Substitution of the oxygen atom in the glycosidic linkage by a disulfide bond or by selenium makes the resulting glycoside resistant to hydrolysis. To clarify the consequences for affinity to lectins we prepared benzene-based mono- to trivalent dithiogalactosides. Inhibitory capacity increased with valency for a plant toxin, the synthetic compounds potently blocking its binding to a lactose-presenting matrix and to cells. Human galectins were much less sensitive to the disulfides than the toxin. This differential response constitutes a beneficial effect to avoid cross-reactivity in vivo. Symmetrical selenodigalactoside and diselenodigalactoside were prepared and similarly tested. Both compounds proved rather equally bioactive for the toxin, graded activity was measured for human galectins. This result directs attention to further studies to relate Se-dependent alterations in bond angle and length as well as van der Waals radius to binding properties of selenoglycosides to biomedically relevant lectins. (C) 2015 Elsevier Ltd. All rights reserved.