Glycoside and peptide clustering around the octasilsesquioxane scaffold via photoinduced free-radical thiol–ene coupling. The observation of a striking glycoside cluster effect

Abstract

Two series of multivalent octasilsesquioxane glyco- and peptido-conjugates were synthesized using the photoinduced free-radical thiol-ene coupling (TEC). The first series was obtained by coupling C-glycosylpropyl thiols and cysteine containing peptides with the known octavinyl octasilsesquioxane while the second series was obtained by reacting glycosyl thiols with a new octasilsesquioxane derivative displaying eight PEGylated chains functionalized with terminal allyl groups. The evaluation of the binding properties of mannoside and glucoside clusters toward Concanavalin A by Enzyme-Linked Lectin Assay (ELLA) revealed a modest glycoside cluster effect. On the other hand, the PEGylated POSS-based glycocluster featuring eight N-acetyl-glucosamine residues showed high affinity toward Wheat Germ Agglutinin to give a measured IC(50) at 3 nM. The calculated relative potency per number of sugar unit (rp/n) was superior to a value of 10(6), thus revealing the occurrence of a striking glycoside cluster effect.

Multivalent Fucosides with Nanomolar Affinity for the Aspergillus fumigatus Lectin FleA Prevent Spore Adhesion to Pneumocytes

“…Dondoni et al. previously showed the versatility of free‐radical thiol‐ene coupling (TEC) to functionalize vinyl‐COSS . The hydrothiolation of the vinyl‐COSS scaffold was efficiently achieved using thiol compound 29 under UV irradiation (Scheme ).…”

Star-Shaped and Linear POSS-Polylactide Hybrid Copolymers

“…The additional advantage of the thiol-ene addition is that it introduces thioether functions to the product, which may be further modified [32]. In most of the published work the thiol-ene click addition process involved reaction of thiols with octavinyl- or octavinyldimethylsilyloxy-POSS [33,34,35,36]. …”

A Click Ligation Based on SuFEx for the Metal‐Free Synthesis of Sugar and Iminosugar Clusters

“…Cognizant of the work of Carreira and co‐workers dealing with the preparation of carbohydrate sulfonyl chlorides bearing an anomeric methylene tether between the sugar moiety and the sulfonyl group, we decided to employ the same strategy as an entry to new carbohydrate sulfonyl halides. Towards this aim, known C ‐glucosylpropyl thioacetate 7 was employed as a starting material (Scheme ). To our great pleasure, this C ‐glycoside, when treated with Oxone, afforded corresponding sulfonate salt 8 in 94 % yield following column chromatography.…”

“…In the same context, commercially available l ‐lysine methyl ester ( 14 ), featuring two primary non‐equivalent amino groups was also used. Indeed, the reaction of 10 with excess lysine 14 dihydrochloride (10 equiv.) and Et 3 N (20 equiv.)…”