Synthesis of dendritic carbohydrate end‐functional polymers via RAFT: Versatile multi‐functional precursors for bioconjugations

Abstract

AbstractWell‐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 ω‐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. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 4302–4313, 2009