Synthesis of Statistical Copolymers Containing Multiple Functional Peptides for Nucleic Acid Delivery
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 NH 2-terminus. Copolymers of HMPA-co-K12 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.
R. N. Johnson et al., "Synthesis of Statistical Copolymers Containing Multiple Functional Peptides for Nucleic Acid Delivery," Biomacromolecules, vol. 11, no. 11, pp. 3007 - 3013, American Chemical Society (ACS), Nov 2010.
The definitive version is available at https://doi.org/10.1021/bm100806h
Materials Science and Engineering
Keywords and Phrases
Copolymerization; Copolymers; Gene therapy; Gene transfer; Nucleic acids, Active peptides; Aqueous condition; Condensed DNA; Controlled molecular weight; Gene Delivery; HeLa cell; Methacrylamides; Multiple species; Polyethylenimines; Salt solution; Side-chain; Small particles; Statistical copolymers, Peptides, copolymer; n (2 hydroxypropyl)methacrylamide; nucleic acid; peptide; polyethyleneimine; DNA; polymer, article; functional assessment; gene targeting; HeLa cell; molecular weight; polymerization; priority journal; chemical structure; chemistry; gene transfer; genetics; HeLa cell line; human; particle size; surface property; synthesis, DNA; Gene Transfer Techniques; HeLa Cells; Humans; Molecular Structure; Molecular Weight; Particle Size; Peptides; Polymerization; Polymers; Surface Properties
International Standard Serial Number (ISSN)
Article - Journal
© 2010 American Chemical Society (ACS), All rights reserved.
01 Nov 2010