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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Modulation of Ascorbic Acid-Induced DNA Cleavage by Polyamide: Cleavage Manner, Kinetics and Mechanism

Author(s): C. Li, S. Duan, J. Xu, R. Qiao, P. Xu and Y. Zhao

Volume 19 , Issue 6 , 2012

Page: [921 - 926] Pages: 6

DOI: 10.2174/092986712799034860

Price: $65


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.

Keywords: Ascorbic acid, DNA cleavage, double-strand, kinetics, mechanism, polyamide, Manipulation of DNA, biotechnology, therapeutics, conjugations

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