Title

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

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 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.

Department(s)

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)

1525-7797

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2010 American Chemical Society (ACS), All rights reserved.

PubMed ID

20923198

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