Nucleic acid cleavage reactions

In these reactions that mediate the nucleic acid cleavage reactions by generation of reactive oxygen species (ROS), unwanted side effects such as lipid peroxidation and free radical induced toxicity may limit their use as has been postulated in case of Fe +/ +-gentamicin complexes. ... 

Water is not just the solvent in which the chemical reactions of living cells occur it is very often a direct participant in those reactions. The formation of ATP from ADP and inorganic phosphate is an example of a condensation reaction in which the elements of water are eliminated (Fig. 2-22a). The reverse of this reaction— cleavage accompanied by the addition of the elements of water—is a hydrolysis reaction. Hydrolysis reactions are also responsible for the enzymatic depolymerization of proteins, carbohydrates, and nucleic acids. Hydrolysis reactions, catalyzed by enzymes called... 

Salomon J, Elad D (1973) Photochemical reactions of nucleic acid constituents. Peroxide-initiated reactions of purines with alcohols. J Org Chem 38 3420-3421 Salomon J, Elad D (1974) Ultraviolet and y-ray-induced reactions of nucleic acid constituents. Reactions of purines with amines. Photochem Photobiol 19 21-27 Samuni A, Neta P (1973) Hydroxyl radical reaction with phosphate esters and the mechanism of phosphate cleavage. J Phys Chem 77 2425-2429... 

Figure 4. Reaction Mechanism for N-Acetoxy Arylamines (V). Ac, acetyl RSCH3 methionine RNH2, N2-guanine-nucleosides, -nucleotides, or -nucleic acids RCH, C8-guanine-nucleo-sides, -nucleotides, or -nucleic acids. Pathways and heterolytic cleavages a and b are discussed in the text. Dashed arrows indicate proposed pathways.

The photolytic activation of 5m was also shown to lead to DNA cleavage [33,35-38]. This reaction appeared to be faster and more efficient than the Cu+-catalyzed cleavage conditions. The mechanism(s) of DNA cleavage should be different because aryl cations (not aryl radicals) are believed to be produced under photolytic conditions (Fig. 12) [7]. Such electrophiles should target the nucleic acid bases and/or the positively charged phosphodiester backbone, and both of these could lead to DNA cleavage. 

Figure 10.13 Phosphoryl-transfer reactions. The figure shows (a) nucleotide polymerization, (b) nucleic acid hydrolysis, (c) first cleavage of an exon-intron junction by group I ribozyme (d) and by a group II ribozyme, (e) strand transfer during transposition and (f) exon ligation during RNA splicing. (From Yang et al., 2006. Copyright 2006, with permission from Elsevier.)...

Any technique designed to characterize binding interactions by determining the accessibility of the backbone of macromolecules to cleavage or modification reactions. For nucleic acid interactions, footprinting was originally accomplished by changes in phosphodiester accessibility to DNase 1, but numerous chemical and enzymatic methods continue to be elaborated. 

Although some depolymerases act processively in cleaving their polymeric substrates, others act by what can be described as multiple attack which results in nonselective scission or random scission. The analysis of cleavage products during the course of enzyme-catalyzed depolymerization can provide important clues about the nature of the reaction. With random scission, the rate of bond scission must be proportional to the total number of unbroken bonds present in the solution. Thomas measured the rate of base addition in a pH-Stat (a device with an automated feedback servomotor that expels ti-trant from a syringe to maintain pH) to follow the kinetics of DNA bond scission by DNase. The number of bonds cleaved was linear with time, and this was indicative of random scission. In other cases, one may apply the template challenge method to assess the processivity of nucleic acid polymerases. See Processivity... 

Metal ions, especially Zn(II), play an important role in many enzyme-catalyzed reactions involving nucleic acids, such as DNA cleavage by zinc nuclease. Therefore, the binding of Zn(II) to a 19-mer double-stranded oligodeoxyribonucleotide was investigated to understand the role of zinc in DNA cleavage catalyzed by mung bean nuclease [107]. 

Despite all of the activity in pyrimidine-based synthesis, only one study has emerged of solid-phase versions of these reactions <2003TL1267, 20030BC1909>. This chemistry was based upon condensation of dicarbonyl compounds with resin-bound pyrimidine-5,6-diamines through a 2-alkylthio link and oxidative cleavage as described in Section 10.18.7.2. The value of alkylthio substituents in the synthesis of complex substituted pterins has also been demonstrated in the synthesis of nucleic acid conjugates <2004OBC3588> (see Section 10.18.12.4). 

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