title: End-functionalized polymers and junction-functionalized diblock copolymers via RAFT chain extension with maleimido monomers.
abstract: A new strategy is described for functionalizing the omega-terminal end of polymers synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization that provides spatially controlled bioconjugation sites. Traditional methods for preparing omega-functional polymers require the reduction of the RAFT chain-transfer agent to yield secondary or tertiary thiols of low reactivity or the synthesis of novel chain-transfer agents that contain reactive groups. As an additional strategy, N-substituted maleimido monomers have been used in a modified block polymerization to add a single maleimido unit onto the RAFT polymer with nearly quantitative efficiency. Unique reactive groups contained in the N-substituent are thereby added to the omega-terminal end of the polymer and are subsequently available for conjugation reactions. This technique has been demonstrated using N-(2-aminoethyl)maleimide trifluoroacetate to introduce a single primary amine to the omega-terminus of poly(dimethylaminoethyl methacrylate) and poly(N-isopropyl acrylamide) and to a specialized block copolymer for siRNA delivery. Evidence for retention of functional RAFT endgroups is provided by synthesis results where chain-extended polyDMAEMA (M(n) = 10 600 g/mol, M(w)/M(n) = 1.14) was used as a macro chain transfer agent for the polymerization of styrene, yielding a diblock polymer of low polydispersity (M(n) = 20 300 g/mol, M(w)/M(n) = 1.11). It is thus also possible to construct diblock copolymers with a bioconjugation site precisely located at the junction between the two blocks. The chain-extended polymers are functionalized with an amine-reactive fluorescent dye or folic acid at conjugation efficiencies of 86 and 94%, respectively. The versatile chain-extension technique described here offers unique opportunities for the synthesis of well-defined polymeric conjugates to molecules of biological and targeting interest.
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Henry
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Convertine
authors.forename: Danielle S W
authors.initials: DS
authors.lastname: Benoit
authors.forename: Allan S
authors.initials: AS
authors.lastname: Hoffman
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Stayton
mesh_terms: D009682:Magnetic Resonance Spectroscopy; D008301:Maleimides / Q000737:chemistry*; D008970:Molecular Weight; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D008301:Maleimides; D011108:Polymers; C043592:maleimide