title: Divergent and convergent synthesis of GalNAc-conjugated dendrimers using dual orthogonal ligations.
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 (compound 13), which demonstrates that the binding properties of these glycoconjugates are strongly dependent on the orientation and distribution of the GalNAc units.
authors.affiliation: Univ. Grenoble Alpes, DCM, 38000 Grenoble, France.
authors.forename: Baptiste
authors.initials: B
authors.lastname: Thomas
authors.forename: Carlo
authors.initials: C
authors.lastname: Pifferi
authors.forename: Gour Chand
authors.initials: GC
authors.lastname: Daskhan
authors.forename: Michele
authors.initials: M
authors.lastname: Fiore
authors.forename: Nathalie
authors.initials: N
authors.lastname: Berthet
authors.forename: Olivier
authors.initials: O
authors.lastname: Renaudet
mesh_terms: D000116:Acetylgalactosamine / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000327:Adsorption / Q000187:drug effects; D000480:Alkynes / Q000737:chemistry; D001386:Azides / Q000737:chemistry; D018360:Crystallography, X-Ray; D061565:Cycloaddition Reaction; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006001:Glycoconjugates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D010091:Oximes / Q000737:chemistry; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D037121:Plant Lectins / Q000737:chemistry; D030262:Soybean Proteins / Q000737:chemistry; D010835:Phytohemagglutinins
chemical_list: D000116:Acetylgalactosamine; D000480:Alkynes; D001386:Azides; D050091:Dendrimers; D006001:Glycoconjugates; D010091:Oximes; D010456:Peptides, Cyclic; D037121:Plant Lectins; D030262:Soybean Proteins; C028824:soybean lectin; D010835:Phytohemagglutinins