Characterization of Interpolyelectrolyte Complexes between Double-Stranded DNA and Polylysine Comb-Type Copolymers Having Hydrophilic Side Chains

The polyionic interaction between DNA and polycations grafted with hydrophilic dextran side chains was evaluated. The comb-type copolymers, poly(l-lysine)-graft-dextran, were successfully prepared by employing a reductive amination reaction between ε-amino groups of poly(l-lysine) (PLL) and the redu...

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Published in:Bioconjugate chemistry 1998-03, Vol.9 (2), p.292-299
Main Authors: Maruyama, Atsushi, Watanabe, Hiromitsu, Ferdous, Anwarul, Katoh, Maiko, Ishihara, Tsutomu, Akaike, Toshihiro
Format: Article
Language:English
Subjects:
Animals
Cations
Cattle
Chemical Phenomena
Chemistry, Physical
Circular Dichroism
Dextrans - chemistry
Dimethyl Sulfoxide
DNA - chemistry
Drug Stability
Electrochemistry
Electrophoresis, Agar Gel
Hot Temperature
Molecular Weight
Nephelometry and Turbidimetry
Nucleic Acid Conformation
Nucleic Acid Hybridization
Osmolar Concentration
Poly dA-dT - chemistry
Polylysine - chemistry
Solubility
Water
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Summary:The polyionic interaction between DNA and polycations grafted with hydrophilic dextran side chains was evaluated. The comb-type copolymers, poly(l-lysine)-graft-dextran, were successfully prepared by employing a reductive amination reaction between ε-amino groups of poly(l-lysine) (PLL) and the reductive ends of dextran (Dex). A coupling efficacy on the order of 70% was obtained regardless of intrinsic philicities of the solvents used, either aqueous buffer or DMSO. The resulting graft copolymers, which varied in the degree of grafting and the length of hydrophilic side chains, formed a soluble complex with DNA. They also affected the melting behavior of double-stranded DNA (dsDNA) in different ways. Copolymers having a high degree of grafting thermally stabilized dsDNA without affecting its reversible transition between single-stranded and double-stranded forms. However, copolymers with a low degree of grafting or with a high degree of grafting of short dextran chains impeded the reversibility of this transistion. Furthermore, highly grafted copolymers also accelerated the hybridization of DNA strands in a low-ionic strength medium. It is of particular note that these copolymers scarcely altered circular dichroismic signals of dsDNA even when the copolymers were added in excess. This suggested that the copolymer interacted with dsDNA without affecting its native structure or physicochemical properties. Finally, the copolymer even formed a stable complex with a short oligonucleotide (20 bases). We, therefore, concluded that, by regulating the degree of grafting and the molecular weight of grafted side chains, it would be possible to design novel different graft copolymers capable of acting as carriers of functional genes to target cells or tissue.
ISSN:1043-1802
1520-4812
DOI:10.1021/bc9701510