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 Mn = 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 ?-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.