Phosphodiester structure

Ribonucleic Acid. A major contribution to the formulation of RNA structure was the demonstration that alkaline hydrolysis of RNA quantitatively liberates about equal amounts of mononucleotide isomers of all four bases 103). Although it was readily established that none of these mononucleotides is the 5 -phosphate isomer, it was not until some years later that Cohn and associates 103) by controlled degradation experiments, and Brown and associates 121) by the synthetic route, established that the products were isomers involving phosphate attachment at positions 2 and 3 of the ribose. Of equal significance was the discovery 161) that hydrolysis of RNA by the enzyme phosphodiesterase (snake venom or intestinal) liberates mononucleotides exclusively of still another type, the 5 -mono-nucleotides. It was thus necessary to establish the mechanisms which could account for one phosphodiester structure in the RNA chain giving rise to three isomers of each mononucleotide. 

Asseline, U., Barbier, C, and Thuong, N, T, (1986) Oligothymidylates with alternating alkyl phosphotriester and phosphodiester structure covalently bonded to an intercalating agent. Phosphorus Sulfur 26 63-73. 

Giles RV, Tidd DM (1992) Increased specificity for antisense oligodeoxynucleotide targeting of RNA cleavage by RNase H using chimeric methylphosphonodiester/phosphodiester structures. Nucleic Acids Res 20 763-770... 

FIGURE 11.18 Furanoses are represented by lines phosphodiesters are represented by diagonal slashes in this shorthand notation for nucleic acid structures. 

Reactive trajectories, 43-44,45, 88,90-92,215 downhill trajectories, 90,91 velocity of, 90 Relaxation processes, 122 Relaxation times, 122 Reorganization energy, 92,227 Resonance integral, 10 Resonance structures, 58,143 for amide hydrolysis, 174,175 covalent bonding arrangement for, 84 for Cys-His proton transfer in papain, 141 for general acid catalysis, 160,161 for phosphodiester hydrolysis, 191-195,... 

The DNA structure involves two polyanionic phosphodiester strands linked together by hydrogen bonding of base pairs. The strands can be separated by a denaturation process (melting). The melting temperatnre increases with an increase in guanine (G)-cytosine (C) content, since this base pair possess three hydrogen bonds as compared to just two for the adenine (A)-thymine (T) pair. 

The base sequence or primary structure of a polynucleotide can be represented as shown below. The phosphodiester bond is represented by P or p, bases by a single letter, and pentoses by a vertical line. 

The double-stranded structure of DNA can be separated into two component strands (melted) in solution by increasing the temperature or decreasing the salt concentration. Not only do the two stacks of bases puU apart but the bases themselves unstack while still connected in the polymer by the phosphodiester backbone. Concomitant with this denaturation of the DNA molecule is an increase in the optical absorbance of the purine and pyrimidine bases—a phenomenon referred to as hyperchromicity of denaturation. Because of the... 

Unlike other enzymes that we have discussed, the completion of a catalytic cycle of primer extension does not result in release of the product (TP(n+1)) and recovery of the free enzyme. Instead, the product remains bound to the enzyme, in the form of a new template-primer complex, and this acts as a new substrate for continued primer extension. Catalysis continues in this way until the entire template sequence has been complemented. The overall rate of reaction is limited by the chemical steps composing cat these include the chemical step of phosphodiester bond formation and requisite conformational changes in the enzyme structure. Hence there are several potential mechanisms for inhibiting the reaction of HIV RT. Competitive inhibitors could be prepared that would block binding of either the dNTPs or the TP. Alternatively, noncompetitive compounds could be prepared that function to block the chemistry of bond formation, that block the required enzyme conformational transition(s) of turnover, or that alter the reaction pathway in a manner that alters the rate-limiting step of turnover. 

The hydrolysis of p-nitrophenyl acetate and bis(p-nitrophenyl phosphate) are frequently used to probe hydrolytic activity. A problem with some other dinuclear systems is that the Zn units are held together by bridging ligands which can be cleaved on reaction with the substrate.440 This is not the case in a ditopic ligand such as those designed by Lippard and co-workers based on Kemp s triacid imide with a xylyl spacer.441,442 Both zinc dimers and mixed metal dimers were formed and a structure characterized with a bridging phosphodiester (Figure 6). 

Figure 6 Molecular structure of a dimeric zinc compound with a bridging phosphodiester formed with...

Fig. 19.1. Structure of phosphorylcholine (PC). PC is involved in phosphodiester linkage to carbohydrate in a number of lower organisms, including filarial nematodes (linking sugar appears to be A/-acetylglucosamine on species examined to date).

Figure 8.5 (a) Structural detail of the 2 -5 oligonucleotides (2 -5 A ) generated by 2 -5 A synthetase. Compare the 2 -5 phosphodiester linkages with the 3 -5 linkages characteristic of normal cellular oligonucleotides such as mRNA (b)... 

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