Recognition of DNA topology in reactions between plasmid DNA and cationic copolymers

This study for the first time demonstrates phenomenon of recognition of DNA tertiary structure by the synthetic polycationic molecules. Effects of DNA topology were evaluated using supercoiled and linearized forms of plasmid DNA (scDNA and lDNA). Recognition is achieved by using relatively simple chemical structures interacting with the DNA. Two polycations modified with water-soluble poly(ethylene glycol) (PEG) chains, PEG- block-poly(N-methyl-4-vinylpyridinium sulfate) (PEC-b-PVP) and PEG -graft-polyethyleneimine (PEG-g-PEI) were used. When added to the mixtures of lDNA and scDNA, PEO-b-PVP selectively bound to scDNA, while lDNA remained free. In contrast, PEO-g-PEI interacted with both forms of the DNA present in the mixture. Distinct behavior of two copolymers was attributed to the differences in their structure, particularly, charge density of the polycation blocks. Relatively small variation in the polycation ionization state can result in drastic changes in its behavior upon interaction with DNA. Particularly, the change of pH from 7.0 to 5.0, increasing the charge density of PEI block in PEO-g-PEI, was also accompanied by the appearance of recognition phenomena. These findings uncover possibilities for the control of the processes of DNA incorporation in the complexes with cationic species by altering the DNA topology, which may have practical significance in using these complexes for gene delivery.