Synthesis of statistical copolymers containing multiple functional peptides for nucleic Acid delivery

Biomacromolecules. 2010 Nov 8;11(11):3007-13. doi: 10.1021/bm100806h. Epub 2010 Oct 5.

Abstract

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 (K12), and an endosomal escape peptide (K6H5) that had been modified with an aminohexanoic linker and capped with methacrylamide vinyl on the NH2-terminus. Copolymers of HMPA-co-K12 and HPMA-co-K12-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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • DNA / administration & dosage*
  • DNA / genetics
  • Gene Transfer Techniques*
  • HeLa Cells
  • Humans
  • Molecular Structure
  • Molecular Weight
  • Particle Size
  • Peptides / chemistry*
  • Polymerization
  • Polymers / chemical synthesis
  • Polymers / chemistry*
  • Surface Properties

Substances

  • Peptides
  • Polymers
  • DNA