Synthesis of Dendritic Carbohydrate End-Functional Polymers via RAFT: Versatile Multi-Functional Precursors for Bioconjugations

Well-defined pyridyl disulfide (PDS) end-functionalized polymer-dendritic carbohydrate scaffolds are reported as novel precursors for the attachment of biomolecules. This synthetic approach combines reversible addition fragmentation chain transfer (RAFT) polymerization and "click" reactions. Poly(N-(2-hydroxypropyl) methacrylamide) (PHPMA) with 2-mercaptothiozalidine end-groups was prepared by RAFT polymerization yielding molecular weights of M-n = 4300 and 9900, both with a polydispersity of less than 1.2. These polymers were then attached to dendritic mannose scaffolds preconstructed via consecutive "click" reactions. Finally, the omega-dithiobenzoate RAFT end-group of PHPMA was modified to yield PDS functionality, by aminolysis in the presence of 2,2'-dithiodipyridine. This PDS end-functionalized PHPMA-dendritic carbohydrate scaffold is a versatile precursor for bioconjugations, as the synthetic procedure can easily accommodate a range of sugar functionalities. In addition, the PDS groups can be used to react with any thiol present in a biomolecule (e.g., cysteine residue in proteins, or -SH terminal nucleotides). To demonstrate the utility of these scaffolds we describe their bioconjugation to short interfering RNA. (C) 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 4302-4313, 2009