Modulation of Ascorbic Acid-Induced DNA Cleavage by Polyamide: Cleavage Manner, Kinetics and Mechanism
Authors: Li, C.; Duan, S.; Xu, J.; Qiao, R.; Xu, P.; Zhao, Y.
Source: Current Medicinal Chemistry, Volume 19, Number 6, February 2012 , pp. 921-926(6)
Publisher: Bentham Science Publishers
Abstract:Manipulation of DNA presents a great interest in biotechnology and therapeutics. The molecules that damage DNA selectively offer new prospects for controlled manipulation of DNA. The conjugations of DNA-code reading molecules such as polyamides to reagents that induce DNA damages provide an approach to reach this goal. In this work, a new compound which contained polyamide and ascorbic acid conjugated by flexible linker (polyamide-Vc), was successfully synthesized, characterized, and evaluated as DNA cleavage agent, compared with that by using ascorbic acid molecule. The kinetics data showed that polyamide-Vc successfully promoted the cleavage of plasmid DNA, with kmax of 0.314 h-1 and Kd of 0.105 mM. The evaluation of DNA linearization elicited that the activity of cleaving double-strand in the supercoiled pUC18 plasmid DNA by polyamide-Vc was enhanced remarkably, achieving n1/n2 ratio of 13.9 at 1.2 mM for 1 h. The introduction of polyamide to Vc could also partially weaken the inhibition of hydrogen radical to double-strand cleavage process because of its good binding activity to DNA. We anticipate that this work could provide a method for improving the efficiency of double-strand cleavage, especially to oxidative cleavage agents.
Document Type: Research Article
Publication date: February 1, 2012
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