DNA-scission

There are, indeed, many biological implications that have been triggered by the advent of fullerenes. They range from potential inhibition of HIV-1 protease, synthesis of dmgs for photodynamic therapy and free radical scavenging (antioxidants), to participation in photo-induced DNA scission processes [156, 157, 158, 159, 160, 161, 162 and 163]. These examples unequivocally demonstrate the particular importance of water-soluble fullerenes and are summarized in a few excellent reviews [141, 1751. 

Investigations of the kinetics of hole transfer in DNA by means of pulse radiolysis of synthetic ODNs have provided details about the hole transfer process, especially over 1 /is, including the multi-step hole transfer process. Based on the investigation of the kinetics of hole transfer in DNA, development of the DNA nanoelectronic devices is now expected. An active application of the hole transfer process is also desirable from a therapeutical point of view, since hole transfer may play a role in improvement of quantum yield and selectivity of DNA scission during photodynamic therapy. The kinetics of the hole transfer process is now being revealed, although there is still much research to be performed in this area. The kinetics of adenine hopping is another area of interest that should be explored in the future. 

Shen T, Hollenberg PF. The mechanism of stimulation of NADPH oxidation during the mechanism-based inactivation of cytochrome P450 2B1 by N-methylcarbazole redox cycling and DNA scission. Chem Res Toxicol 1994 7(2) 231-238. 

O Neill P, Parker AW, Plumb MA, Siebbeles LDA (2001) Guanine modifications following ionization of DNA occurs predominantly via intra- and not interstrand charge migration an experimental and theoretical study. J Phys Chem B 105 5283-5290 Offer T, Samuni A (2002) Nitroxides inhibit peroxyl radical-mediated DNA scission and enzyme inactivation. Free Radical Biol Med 34 672-881... 

The importance of artificial restriction enzymes has been well understood by many chemists, and several challenging attempts have been made already. Although many difficulties remain, elegant work by many people is paving the way. This chapter deals mainly with the recent work of our laboratory on site-selective DNA scission and its applications to biotechnology. 

This covalent" strategy is very successful for site-selective DNA scission. However, the scission is not sufficiently efficient and must be promoted for practical applica-... 

To accomplish site-selective DNA scission using the non-covalent strategy, we need both (i) molecular scissors that show sufficiently high substrate-specificity and (ii) hot spots" that are formed at predetermined positions in substrate DNA and are hydrolyzed preferentially by these molecular scissors. 

Essential Role of Cap-structure for the Site-selective DNA Scission... 

The present site-selective scission proceeds by an hydrolytic pathway, as is the case in DNA scission by nucleases. Thus, the scission fragments can be recombined with various oligonucleotides by using DNA ligase. Figure 7.6 depicts a typical example. 

Design of Artificial Restriction Enzymes for Double-stranded DNA Scission... 

In isolated rat nuclei, SOD inhibits bleomycin-induced membrane peroxidation, but has no effect on bleomycin-catalysed DNA scission [57]. Thus, it may be possible to use iron chelators to reduce the toxic extracellular side effects of these drugs, whilst leaving the intracellular therapeutic mode of action unaltered. In fact, it has been demonstrated that the cardiotoxicity of adriamycin can be inhibited by the chelating agent ICRF-187 [60],... 

The products of hydroxyl radical-mediated DNA scission (Dizda-roglu, 1986 Von Sonntag, 1987) include (Fig. 8.2) 5,6-dihydrothymine,... 

Antitumor antibiotic, causes single- and double-strand DNA scission (free-radical mediated) inhibition of protein, DNA, and RNA synthesis... 

Tagaya M, Liu K F, Copeland B, et al. (1997). DNA scission after focal brain ischemia temporal differences in two species. Stroke. 28 1245-1254. 

Meijler MM, Zelenko O, Sigman DS. Chemical mechanism of DNA scission by (l,10-phenanthioline)copper carboxyl oxygen of 5-methylenefuranose is derived from water. J/Im Chem Soc. 1997 119 1135-1136. 

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