Divergent and convergent synthesis of GalNAc-conjugated dendrimers using dual orthogonal ligations. Issue 47 (14th October 2015)

• Record Type: Journal Article
• Authors: Thomas, Baptiste; Pifferi, Carlo; Daskhan, Gour Chand; Fiore, Michele; Berthet, Nathalie; Renaudet, Olivier
• Is Part Of: Organic & biomolecular chemistry. Volume 13:Issue 47(2015)
• Page Start: 11529
• Page End: 11538
• Publication Date: 2015-10-14
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c5ob01870f
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : We report a synthetic strategy to prepare hexadecavalent glycodendrimers that can be used in both divergent and convergent route with similar efficiency. Abstract : The synthesis of glycodendrimers remains a challenging task. In this paper we propose a protocol based on both oxime ligation (OL) to combine cyclopeptide repeating units as the dendritic core and the copper(i )-catalyzed azide–alkyne cycloaddition (CuAAC) to conjugate peripheral α and β propargylated GalNAc. By contrast with the oxime-based iterative protocol reported in our group, our current strategy can be used in both divergent and convergent routes with similar efficiency and the resulting hexadecavalent glycodendrimers can be easily characterized compared to oxime-linked analogues. A series of glycoconjugates displaying four or sixteen copies of both α and β GalNAc have been prepared and their ability to inhibit the adhesion of the soybean agglutinin (SBA) lectin to polymeric-GalNAc immobilized on microtiter plates has been evaluated. As was anticipated, the higher inhibitory effect (IC50 = 0.46 μM) was measured with the structure displaying αGalNAc with the higher valency (compound13 ), which demonstrates that the binding properties of these glycoconjugates are strongly dependent on the orientation and distribution of the GalNAc units.