Thiyl Glycosylation of Propargylated Octasilsesquioxane: Synthesis and Lectin-Binding Properties of Densely Glycosylated Clusters on a Cubic Platform

Alberto Marra (1, 2) , Samuele Staderini (2) , Nathalie Berthet (3) , Pascal Dumy (4, 1) , Olivier Renaudet (3) , Alessandro Dondoni (2)

1 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]
2 Laboratorio di Chimica Organica
3 DCM - I2BM - Département de Chimie Moléculaire - Ingéniérie et Intéractions BioMoléculaires
4 LEDSS - Laboratoire d'études dynamiques et structurales de la sélectivité

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

Mots clés: Carbohydrates; Cluster compounds; Glycoconjugates; Click chemistry; Radical reactions; Alkynes; Photochemistry

Domaines: Chimie

Alberto Marra, Samuele Staderini, Nathalie Berthet, Pascal Dumy, Olivier Renaudet, et al.. Thiyl Glycosylation of Propargylated Octasilsesquioxane: Synthesis and Lectin-Binding Properties of Densely Glycosylated Clusters on a Cubic Platform. European Journal of Organic Chemistry, 2013, 2013 (6), pp.1144 - 1149. ⟨10.1002/ejoc.201201453⟩. ⟨hal-01653059⟩