Thiyl glycosylation of propargylated octasilsesquioxane: Synthesis and lectin-binding properties of densely glycosylated clusters on a cubic platform

Abstract

A new polyhedral oligomeric silsesquioxane (POSS) derivative with a periphery of eight PEGylated chains functionalized with terminal propargyl groups was synthesized starting from commercially available octavinyl-POSS. The photoinduced free-radical coupling of this octapropargyl POSS derivative with various sugar thiols enabled the preparation of globular hexadecavalent glycoclusters. Thus, it appears that according to the alkyne hydrothiolation mechanism, two thiyl radicals were added across each triple bond of the POSS scaffold side-chains. The affinities of some of the densely glycosylated clusters towards certain lectins were measured by the Enzyme-Linked Lectin Assay (ELLA). The binding selectivity of Concanavalin A between the hexadecavalent mannosylated and glucosylated clusters was much higher than the selectivity observed for the corresponding octavalent glycoclusters (ref.4). Moreover, the affinity of the N-acetylglucosamine-based cluster towards wheat germ agglutinin (WGA) revealed a remarkable glycoside cluster effect with up to a 9.0 × 105-fold increase in binding compared to monovalent GlcNAc. As a multivalent effect of the same order of magnitude was reported for an octavalent GlcNAc cluster towards the same lectin (ref.4), it is concluded that increasing the number of sugar units around the cubic platform does not lead systematically to an enhancement of binding affinity. Typical hexadecavalent glyco-POSS prepared by thiol-yne coupling. A measured IC50 of 2 nM was found by ELLA with tetrameric wheat germ agglutinin (WGA). Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.