Oligonucleotides phosphodiester

Fig 4 Alternate plumbing diagram for the automated synthesis of oligonucleotide phosphodiesters and phosphorothioates. This scheme also incorporates an output for a capping reagent... 

Oligonucleotides contain about 50 or fewer nucleotides held together by phosphodiester links polynucleotides can contain thousands of nucleotides... 

Modification of the Phosphodiester Backbone. Oligonucleotides having modified phosphate backbones have been extensively studied (46). Because altering the backbone makes derivatives generally more resistant to degradation by cellular nucleases, these materials have the potential to be more resilient antisense dmgs. 

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. 

Other problems arise when modified oligonucleotides are synthesized. Oligonucleotides are most commonly synthesized today for pharmaceutical purposes in the form of phosphorothioates (PS), in which sulfurization of the phosphodiester bond has taken place (Figure 1). 

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)... 

Modified coherence length, 23 806 Modified copper-zinc, nominal composition and UNS designation, 7 722t Modified oligonucleotides, 17 626-637 applications of, 17 626-628 Modified phosphodiester backbones, 17 628-629... 

A variety of such phosphorothioate oligonucleotides have, thus, been reported in the literature [138-142], In one particularly illustrative study, the 20-mer phosphodiester oligonucleotide 5 -TCATGCTCATGCGCTCATGC-3 and its phosphorothioate congener were compared for their distribution... 

An excision endonuclease (excinudease) makes nicks in the phosphodiester backbone of the damaged strand on both sides of the thymine dimer and removes the defective oligonucleotide. 

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