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Convergent Assembly and Surface Modification of Multifunctional Dendrimers by Three Consecutive Click Reactions

Authors

  • Petr A. Ledin,

    1. Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens GA 30602 (USA), Fax: (+1) 706-542 4412
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  • Dr. Frédéric Friscourt,

    1. Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens GA 30602 (USA), Fax: (+1) 706-542 4412
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  • Dr. Jun Guo,

    1. Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens GA 30602 (USA), Fax: (+1) 706-542 4412
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  • Prof. Geert-Jan Boons

    Corresponding author
    1. Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens GA 30602 (USA), Fax: (+1) 706-542 4412
    • Complex Carbohydrate Research Center, University of Georgia, 315 Riverbend Road, Athens GA 30602 (USA), Fax: (+1) 706-542 4412
    Search for more papers by this author

Abstract

Multifunctional dendrimers bearing two or more surface functionalities have the promise to provide smart drug delivery devices that can for example combine tissue targeting and imaging or be directed more precisely to a specific tissue or cell type. We have developed a concise synthetic methodology for efficient dendrimer assembly and heterobifunctionalization based on three sequential azide–alkyne cycloadditions. The methodology is compatible with biologically important compounds rich in chemical functionalities such as peptides, carbohydrates, and fluorescent tags. In the approach, a strain-promoted azide–alkyne cycloaddition (SPAAC) between polyester dendrons modified at the focal point with an azido and 4-dibenzocyclooctynol (DIBO) moiety provided dendrimers bearing terminal and TMS-protected (TMS=trimethylsilyl) alkynes at the periphery. The terminal alkynes were outfitted with azido-modified polyethylene glycol (PEG) chains or galactosyl residues by using CuI-catalyzed azide–alkyne cycloadditions (CuAAC). Next, a one-pot TMS deprotection and second click reaction of the resulting terminal alkyne with azido-containing compounds gave multifunctional dendrimers bearing complex biologically active moieties at the periphery.

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