4.7 Article

Synthesis of Statistical Copolymers Containing Multiple Functional Peptides for Nucleic Acid Delivery

Journal

BIOMACROMOLECULES
Volume 11, Issue 11, Pages 3007-3013

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/bm100806h

Keywords

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Funding

  1. NSF [CBET-0448547]
  2. NIH/NINDS [1R01NS064404]

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Our report describes RAFT copolymerization of multiple species of active peptide monomers with N-(2-hydroxypropyl(methacrylamide) (HPMA) under aqueous conditions. Resulting statistical copolymers are narrowly disperse with highly controlled molecular weight and composition. Side-chain peptide copolymers were synthesized using a DNA condensing peptide (K-12), and an endosomal escape peptide (K6H5) that had been modified with an aminohexanoic linker and capped with methacrylamide vinyl on the NI-I terminus. Copolymers of HMPA-co-K-12 and HPMA-co-K-12-co-K6H5 efficiently condensed DNA into small particles that maintain size stability even in 150 mM salt solutions. With increasing peptide content, the peptide-based polymers demonstrated gene delivery efficiencies to HeLa cells that were comparable to branched polyethylenimine.

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