Phosphodiester, synthesis

U. Kaatze, S.C. Muller and H. Eible, Monoalkyl phosphodiesters synthesis and dielectric relaxation of solutions, Chem. Phys. Lipids 27 (1980) 263-280. 

Of course, as with peptide bond formation, work must be done and so an activation process is necessary. A phosphodiester synthesis would not be possible by merely mixing phosphoric acid with the appropriately protected nucleosides. Finally, as will be discussed later, it may even be desirable to consider protection of the phosphate function. While this is not necessary (and was not done in the initial nucleotide synthesis), it is advantageous and is presently the most accepted protocol. 

The fundamental problem of oligodeoxyribonucleotide synthesis is the efficient formation of the intemucleotidic phosphodiester bond specifically between C-3 and C-5 positions of two adjacent nucleosides. Any functional group (NH of nucleic base the other OH of deoxy-... 

In the diester method a deoxynucleoside-5 -monophosphate is condensed with the 3 -OH group of a deoxynucleotide to produce a 3, 5 -phosphodiester. This is illustrated by a general method for dinucleotide synthesis developed by H.G. Khorana (K.L. Agarwal, 1976). One N-... 

Phosphorothioates. All three synthetic approaches appHcable to unmodified oligonucleotides can be adapted for synthesis of phosphorothioates (11) (33,46). If all of the phosphodiester linkages in an oligonucleotide are to be replaced with phosphorothioates, the ff-phosphonate method for coupling, followed by oxidation with Sg in carbon disulfide and triethylamine in the final step, is the most straightforward method. 

The process of RNA synthesis in bacteria—depicted in Figure 37-3—involves first the binding of the RNA holopolymerase molecule to the template at the promoter site to form a PIC. Binding is followed by a conformational change of the RNAP, and the first nucleotide (almost always a purine) then associates with the initiation site on the 3 subunit of the enzyme. In the presence of the appropriate nucleotide, the RNAP catalyzes the formation of a phosphodiester bond, and the nascent chain is now attached to the polymerization site on the P subunit of RNAP. (The analogy to the A and P sites on the ribosome should be noted see Figure... 

Quinone methides have been shown to be important intermediates in chemical synthesis,1 2 in lignin biosynthesis,3 and in the activity of antitumor and antibiotic agents.4 They react with many biologically relevant nucleophiles including alcohols,1 thiols,5-7 nucleic acids,8-10 proteins,6 11 and phosphodiesters.12 The reaction of nucleophiles with ortho- and /iara-quinone methides is pH dependent and can occur via either acid-catalyzed or uncatalyzed pathways.13-17 The electron transfer chemistry that is typical of the related quinones does not appear to play a role in the nucleophilic reactivity of QMs.18... 

G. Pourceau, A. Meyer, J.-J. Vasseur, and F. Morvan, Combinatorial and automated synthesis of phosphodiester galactosyl cluster on solid support by click chemistry assisted by microwaves, J. Org. Chem., 73 (2008) 6014—6017. 

F. Morvan, A. Meyer, A. Jochum, C. Sabin, Y. Chevolot, A. Imberty, J.-P. Praly, J.-J. Vasseur, E. Souteyrand, and S. Vidal, Fucosylated pentaerythrityl phosphodiester oligomers (PePOs) Automated synthesis of DNA-based glycoclusters and binding to Pseudomonas aeruginosa lectin (PA-IIL), Biocon-jug. Chem., 18 (2007) 1637-1643. 

The enzymes catalysing the synthesis of RNA, using DNA as a template, are known as DNA-dependent RNA polymerases. The term dependency indicates a requirement for a template. The RNA polymerases synthesise RNA in the 5 to 3 direction in formation of the phosphodiester linkage. This requires that the DNA template is read in the 5 to 3 direction (see below for explanation). 

---