Inhibition of nonenzymatic depurination of nucleic acids by polycations

多聚阳离子对核酸非酶促脱嘌呤的抑制作用

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Abstract

DNA base depurination is one of the most common forms of DNA damage in vivo and in vitro, and the suppression of depurination is very important for versatile applications of DNA in biotechnology and medicine. In this work, it was shown that the polycations chitosan (Cho) and spermine (Spm) strongly inhibit DNA depurination through the formation of polyion complexes with DNA molecules. The intramolecular electrostatic interaction of positively charged polycations with DNA efficiently suppresses the protonation of purine groups, which is the key step of depurination. Importantly, the optimal pH for Cho's inhibition of depurination is significantly different from that of Spm. Cho is very effective in the inhibition of depurination in highly acidic media (pH: 1.5-3), whereas Spm is found to suppress the chemical reaction near neutral pH, as well as in acidic solutions. This remarkable pH specificity of the two biorelevant polycations is attributed to the difference in the pK(a) values of the amino groups. The relevance of our results with the biological roles of biogenic polycations is also discussed.

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