Nucleic acid analogues

Since nucleic acids and enzymes play such a large role in chromosome replication during mitosis, a considerable amount of research has been conducted in this area to control viruses. On the molecular level, analogues of nucleic acids are capable of forming complexes with adenine, cytosine, uracil, thymine, and guanine. Through complexation, these nucleic acid analogues are potential inhibitors of biosyntheses that require nucleic acids as templates. 

The minimal cell, as the simplest system which has all the required properties of life (metabolism, self-reproduction and the ability to evolve), is presently studied as part of a new research discipline synthetic biology. This includes subjects such as synthesis in branches of biological systems, for example, of new RNA species, new peptides and new nucleic acid analogues, as well as the synthesis of peptide nucleic acids. One example is the work of M. R. Ghadiri and G. von Kiedrowski on self-replication of oligonucleotides and oligopeptides (Luisi, 2006b). 

Pardridge, W.M., Boado, R.J. and Kang, Y.-S. (1995) Vector-mediated delivery of a polyamide ( peptide ) nucleic acid analogue through the blood-brain barrier in vivo. Proc. Natl. Acad. Sci. USA, 92, 5592-5596. 

Programs that combine the exploration of potential metabolic cycles with the synthetic biology of unnatural nucleic acid analogues and their building blocks and that use the results to guide the design of instruments ... 

Other backbone replacements displayed pairing strengths comparable with that seen in RNA but did not cross-bind with natural RNA and DNA. The exceptional cases are the locked nucleic acids of Wengel et al.11 and the threose nucleic acid analogues of Krishnamurthy and Eschenmoser.12... 

Sreenivasachary N et al (2006) DyNAs constitutional dynamic nucleic acid analogues. Chem Eur J 12 8581-8588... 

A number of other locked nucleosides have been studied, and Imanishi and Obika have reviewed a series of bridged nucleic acid analogues.2 -D,4 -C-ethylene (53) and propylene analogues also have C3 -endo conformations and... 

Other methods are available that vary in their degree of success. These include passage in athymic nude mice (Van Diggelen et al., 1977), growth of cells in rabbit or guinea pig serum (Nair, 1985) and the use of nucleic acid analogues (Marcus et al., 1980)... 

The structure of an oligonucleotide designed to assemble a 4-way junction has been investigated by Preliminary results in the structure determination of nucleic acid analogues containing... 

Nucleoside and nucleic acid analogues, inch peptide nucleic acids, but excluding phosphate replacements 460... 

Imanishi has reported the synthesis and properties of a bridged nucleic acid analogue which contained a N3 P5 phosphoramidate linkage. " The heterodimer containing 3 -amino-2, 4 -BNA thymine monomer and thymine and methylcytosine monomers of 3 -amino-2, 4 -BNA and their 5 -phosphoramidites [34a-c] were synthesised from the intermediate 3 -azido 3 -deoxy-2, 4 -bicyclic thymidine. 

PepNAs are achiral and insensitive to CD, but optically pure polyamide nucleic acid analogues were also reported. Monomer 28 (Scheme 8) has naturally occurring amino acid units, which will confer chirality on the resulting polymers [65]. Although stereocenters on the backbones were expected to influence the complexation of the PepNAs, no details were reported. Polymer 29... 

A detailed analysis of the involvement of microtubules in cytopathic effects was made by Ebina et al. (1978) who infected cells with poliovirus, Sendai virus, adenovirus, and herpesvirus in order to examine the effect of each virus on the formation of microtubular par-acrystals induced by vinblastine sulfate in HeLa-S3 cells. In polio-virus-infected cells, the cytopathic effect (cell rounding) and inhibition of paracrystal formation were both noted at 4 hr postinfection, proceeding in parallel. In the case of Sendai virus infection, no effect on paracrystal formation could be noted despite a syncytial cytopathic effect. In adenovirus- and herpesvirus-infected cells, inhibition of paracrystal formation occurred well before the cytopathic effect and was not blocked by UV irradiation or nucleic acid analogues but was by inhibition of protein synthesis. These findings led Ebina et al. (1978) to the hypothesis that early viral proteins are responsible for inhibition of microtubule formation and the cytopathic effect (cell rounding) except that Sendai virus did not cause this type of cytopathology. 

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). 

There are a number of possible ways to stabilize sugars the most interesting one is to attach the sugar to a purine or pyrimidine, i.e., by converting the carbohydrate to a glycoside, but the synthesis of nucleosides is difficult under plausible prebiotic conditions. It has therefore been suggested that ribonucleotides could not have been the first components of prebiotic informational macromolecules (59). This has led to propositions of a number of possible substitutes for ribose in nucleic acid analogues, in what has been dubbed the "pie-RNA World" (60). 

J. E. Summerton, Stereoregular polynucleotide binding polymers, PCT Int. Appl. WO 86/05518, 25 September 1986 E.P. Sdrchak, J.E. Summerton, and D.D. Weller, Uncharged stereoregular nucleic acid analogues, J. Org. Chem. 52 4202 (1987). 

Miller PS, Yano J, Yano E et al (1979) Nonionic nucleic acid analogues. Synthesis and characterization of dideoxyribonucleoside methylphosphonates. Biochemistry 18 5134-5143... 

Abdur Rahman SM, Sato H, Tsuda N et al (2010) RNA interference with 2, 4 -bridged nucleic acid analogues. Bioorg Med Chem 18 3474—3480... 

Abbas S, Hayes CJ. A novel palladium-catalyzed coupling strategy for the rapid synthesis of nucleic acid analogues bearing modified backbones. Synlett 1999 7 1124-1126. 

---