Accelerated Synthesis of Surface Functionalized Mannosylated Dendrimers Built on Cyclotriphosphazene Core
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MRS Advances © 2019 Materials Research Society DOI: 10.1557/adv.2019.375
Accelerated Synthesis of Surface Functionalized Mannosylated Dendrimers Built on Cyclotriphosphazene Core Lamyaa M. Sallam,1 Tze Chieh Shiao,1 Celia Sehad,1 Abdelkrim Azzouz,1 and René Roy1,2,3* 1 Department of Chemistry, Université du Québec à Montréal, P.O. Box 8888, Succ. Centre-Ville, Montréal, Québec H3C 3P8, Canada
2 INRS-Institut Armand-Frappier, Université du Québec, 531 boul. des Prairies, Laval, Québec, H7V 1B7, Canada
3
Glycovax Pharma Inc., 424 Guy, Suite 202, Montreal, Quebec, H3J 1S6, Canada
* Corresponding author: [email protected] ; Tel.: +1 438-393-5009
ABSTRACT
The syntheses of five propargylated dendrimer scaffolds ranging from 2, 3, 4, 6, and 12 surface groups are described together with a 2-azidoethyl α-D-mannopyranoside. The former is appended to the core structure using highly efficient copper-catalysed azide-alkyne cycloaddition (CuAAC) (“click reaction”) to provide glycodendrimers in an accelerated approach. Two of the core structures are based on cyclotrisphosphazene, thus expanding the scope of the “onion-peel” strategy to build dendritic architectures with a large number of surface groups at the G1 generation only.
INTRODUCTION Simple glycomimetics [1], together with more complex glycoconjugate architectures [2-4] possessing α-D-mannopyranoside and other sugar residues, have been the subjects of numerous reports owing to their widespread implications in human diseases [5]. In this regards, sugar residues have been extensively appended onto, polymers (glycopolymers) [6-7], glycodendrimers [8,9], proteins [10], fullerenes [11],
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graphene [12], liposomes [13], dendrimersomes [14-16], gold nanoparticles[17], and so on. As protein conjugates, so-called neoglycoconjugates [4, 10], the resulting biomaterials have been used as anti-bacterial and anti-cancer vaccines [18-21]. α-DMannopyranosides, including oligosaccharides, are ubiquitous on both pathogens such as HIV gp120 [22], dengue [23] and Ebola viruses glycoproteins [24] and similarly on human epithelial tissues such as uroplakin Ia [25]. Paradoxically, both pathogens and human cells contain receptors for these sugar derivatives. Therefore, the design of antagonists against these receptors have to be carefully taken into considerations the problems of “on and off” targets [1]. We previously described several dendrimers having mannosides on the surface [9, 26, 27]. Particularly appealing were those architectures that did not follow the usual path of dendrimers constructions such as PAMAM [28], PEI [29], and those based on Boltorn [30], simply because they are initiated from A2-type cores onto which are sequentially and repetitively added AB2 monomers. These approaches greatly limit the full potential of dendrimers while taki
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