Sugar-Phosphate Backbone Analogues

Peptide nucleic acid (PNA) is another analogue of RNA and DNA that has been considered as a potential ancestor of present day nucleic acids. In this molecule the natural sugar-phosphate backbone has been replaced by peptide-like linkages [218]. In recent years, novel syntheses of PNA have been reported mainly focused on their application for antisense and antigene therapies [219]. The physical-chemical properties of PNA make it both... 

The so-called peptide nucleic acids (PNAs) 2.67 (140-142) are examples of the replacement of the entire sugar-phosphate backbone with different functionah-ties that retain biological activity. The chemistry is similar to SP peptide synthesis employing Boc or Fmoc protocols (see Section 2.1). Peptide-ON hybrids, where either one (143) or two (144) of the ON termini are attached to peptide chains, have been reported. Acyclic silicon phosphoramidites 2.68 (145) have also been used for SPS of silicon-containing ON analogues. 

Both L- and D-ribose occur in this complex mixture, but are not particularly abundant. Since all carbohydrates have somewhat similar chemical properties, it is difficult to envision simple mechanisms that could lead to the enrichment of ribose from this mixture, or how the relative yield of ribose required for the formation of RNA could be enhanced. However, the recognition that the biosynthesis of sugars leads not to the formation of free carbohydrates but of sugar phosphates, lead Albert Eschenmoser and his associates to show that under slightly basic conditions the condensation of glycoaldehyde-2-phosphate in the presence of formaldehyde considerable selectivity exist in the synthesis of ribose-2,4-diphosphate 54). This reaction has also been shown to take place under neutral conditions and low concentrations in the presence of minerals (55), and is particularly attractive given the properties of pyranosyl-RNA (p-RNA), a 2 ,4 -linked nucleic acid analogue whose backbone includes the six-member pyranose form of ribose-2,4-diphosphate 56). 

Peptide nucleic acid (PNA) probes as a DNA analogue that possess an uncharged pseudopeptide backbone instead of the charged phosphate-sugar backbone of natural DNA and, consequently, greater affinity to complementary DNA and better distinction between closely related sequences [33]. 

Generally PNAs have modified polymer backbones (phosphate groups and sugar moieties) and/or modified nucleic acid bases. These analogues can be classified by their preparation methods ... 

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