Hydrolytic cleavage of nucleic acids

The cleavage of a P-0 bond of phosphomono- or diesters results in a nucleophilic substitution on the scissile phosphate. This is a true hydrolysis if a water molecule is the attacking nucleophile, or a transesterification when the nucleophile is an alcohol. These two formally distinct reactions will be discussed in this section, which is devoted to hydrolytic cleavage of nucleic acids and models, in contrast to the oxidative cleavage described in Section II. 

Adenine (29, 6-aminopurine) and guanine (8, 2-amino-6-hydroxypurine) are obtained from the hydrolytic cleavage of nucleic acids (see below). Deamination with HNO2 converts adenine into hypoxanthine, and guanine into xanthine. 

The hydrolytic degradation of nucleic acids is catalyzed by nucleases, which are phosphodiesterases because they cleave the phosphodiesteric bonds hydrolytically (Linn et al., 1993). The cleavage can potentially occur on either side of the phosphorus atom, i.e. on the 3 -side (a) and the 5 -side (b) ... 

In a given phosphodiester bond, hydrolytic enzymatic cleavage can occur at two locations, indicated by p and d in Figure 10.16. The former is proximal with respect to the 3 -OH group the latter is distal with respect to the 3 -OH. Enzymes that catalyze the hydrolysis of nucleic acids are nucleases (see Table 10.2). Exonucleases remove nucleotides (or nucleosides) from either the 5 or the 3 end of the polynucleotide. These are specific for either the p or the d bond. Thus, an exo-... 

Because of their aromatic structures, the purine and pyrimidine bases absorb UV light. At pH 7 this absorption is especially strong at 260 nm. However, when the nitrogenous bases are incorporated into polynucleotide sequences, various noncovalent forces promote close interactions between them. This decreases their absorption of UV light. This hypochromic effect is an invaluable aid in studies involving nucleic acid. For example, absorption changes are routinely used to detect the disruption of the double-stranded structure of DNA or the hydrolytic cleavage of polynucleotide strands by enzymes. 

Hydrolytic cleavage of N,0-acetals due to enzymatic processes leads to nucleic acid chain elements without a nucleobase. Such positions are potential mutation sites. To study such mechanisms and to induce directed mutagenesis, oligonucleotides have been synthesized containing tetrahydrofuran building blocks introduced via corresponding phosphoramidites [310,311] (Fig. 35). 

Nucleotides - Compounds formally obtained by esterification of the 3 or 5 hydroxy group of nucleosides with phosphoric acid. They are the monomers of nucleic acids and are formed from them by hydrolytic cleavage. [5]... 

Enzymatic polymerization is carried out by DNA and RNA polymerases, both of which carry out pyrophos-phorolysis, i.e., cleavage of a high energy pyrophosphate bond coupled to esterification of 5 phosphate linked to the 3 -OH of the previous residue. The reaction is reversible, although it strongly favors synthesis. Degradation of nucleic acids is not due to reversal of the reaction, but rather a hydrolytic reaction catalyzed by nucleases, namely, RNases and DNases, which generate nucleotides or deoxynucleotides, respectively. 

Various metals have been complexed to oligonucleotides to produce hydrolytic or oxidative cleavage of a target nucleic acid. Lanthanide complexes covalently attached to oligonucleotides are known to cleave single-stranded... 

Nucleases a group of hydrolytic enzymes which cleave nucleic acids. Exonucleases attack the nucleic acid molecule at its terminus, whereas endonucleases are able to catalyse a hydrolytic cleavage within the polynucleotide chain. Deoxyribonucleases (DNAases) are specific for DNA, ribonucleases (RNAases) for RNA. All N. are Phosphodiesterases (see) they catalyse the hydrolysis of either the 3 or 5 bond of the 3, 5 -phosphodiester linkage. Ribonuclease (see) has been extensively studied. 

Mancin F, Tecdla P. Zinc(II) complexes as hydrolytic catalysts of phosphate diester cleavage from model substrates to nucleic acids. NewJ Chem. 2007 31 800-817. Parkin G. Synthetic analogues relevant to the strucmre and function of zinc enzymes. Chem Rev. 2004 104 699-767. 

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