Proper folding and assembling are essential for biopolymers to exhibit their inherent biological activities. In living system, molecular chaperones support precise folding of proteins and nucleic acids. We have designed ionic graft copolymers consisting of a polyion backbone and hydrophilic graft chains to engineer folding and assembling of biopolymers such as DNA and peptides having opposite ionic charges. The cationic copolymer formed soluble inter-polyelectrolyte complex with DNA and acidic peptides. The copolymers significantly facilitate DNA assembly including DNA duplex, triplex and quadruplex formations and exhibit nucleic acid chaperone-like activity. The activity of the copolymer was applied to DNA analysis including genotyping methods and DNA nanotechnology. We recently showed that the copolymer enhanced activity of DNA enzyme (DNAzyme) over a wide temperature range under multiple-turnover conditions (1). Activity of an allosteric DNAzyme, MNAzyme, was also increased by the copolymer (2). The cationic graft copolymers effectively induced random-to-helix transition of an acidic peptide, E5, having membrane-disrupting activity. The copolymer/peptide mixture showed stronger membrane disrupting activity than peptide alone at acidic pH. Of interest, the copolymer is capable of activating the peptide at neutral pH, where the peptide also is inactive (Fig. 1) (3). These findings would be crucial to design functional liposomes and delivery tools to cytosols. 1, J. Gao et al., Biomater. Sci., 3, 308-316 (2015) 2, J. Gao et al., Biomater. Sci, 3, 716-720 (2015) 3, N. Shimada et al., J. Controlled Rel., in press.

Polymer materials to fold and activate functional DNA and peptides

251st National Meeting (2016)

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