Dendri-RAFTs: a second generation of cyclopeptide-based glycoclusters.

Synthetic glycoclusters and their related biol. applications have stimulated increasing interest over the last decade. As a prerequisite to discovering active and selective therapeuticals, the development of multivalent glycoconjugates with diverse topologies is faced with inherent synthetic and structural characterization difficulties. Here we describe a new series of molecularly-defined glycoclusters that were synthesized in a controlled manner using a robust and versatile divergent protocol. Starting from a Regioselectively Addressable Functionalized Template (RAFT) carrier, either a polylysine dendritic framework or a second RAFT, then 16 copies of $\beta$Gal, $\alpha$Man, $\beta$Lac or cancer-related Thomsen-Freidenreich ($\alpha$TF) antigen were successively conjugated within the same mol. using oxime chem. We thus obtained a new generation of dendri-RAFT glycoclusters with high glycosidic d. and variable spatial organizations. These compds. displaying 16 end-groups were unambiguously characterized by NMR spectroscopy and mass spectrometry. Further biol. assays between a model lectin from Canavalia ensiformis (ConA) and mannosylated glycoclusters revealed a higher inhibition potency than the tetravalent counterpart, in particular for the hexadecavalent polylysine skeleton. Together with the efficiency of the synthetic and characterization processes, this preliminary biol. study provided clear evidence of promising properties that make the second generation of cyclopeptide-based glycoclusters attractive for biomedical applications. [on SciFinder(R)]


Dendri-RAFTs: a second generation of cyclopeptide-based glycoclusters.
Type de publication
Article de revue
Année de publication
Org. Biomol. Chem.
Soumis le 12 avril 2018