Nucleic acid analogues

Nucleic acid analogues are compounds structurally similar to naturally occuring RNA and DNA, used as a research tool in molecular biology and/or as cure in medicine.

Medicine

Main article: Nucleoside analogues Several nucleoside analogues are used as antiviral or anticancer agents. The viral polymerase incorporates these compounds with non-canon bases. These compounds are activated in the cells by being converted into nucleotides, they are adminisered as nuclosides as charged nucleotides cannot easily cross cell membranes.

Molecular biology

Several artificial forms of nucleic acid chains are used for various purposes, such as FISH or RNAi. The most common are locked nucleic acid (LNA), morpholino, peptide nucleic acid (PNA). These bind according to Watson and Crick pairing with RNA or DNA, but are immune to nuclease activity (RNA is too unstable). They generally cannot be enzymatically synthesised and can only be produced synthetically. These oligonucleotides differ as they have a different backbone sugar.

In sequencing dideoxynucleotides are used. These nucleotide triphosphates posses a non-canon sugar, dideoxyribose which lacks 3' hydroxyl group (which accepts the phosphate) and therefore cannot bond with the next base, terminating the chain as the DNA polymerases mistake it for a regular deoxyribonucleotide. The nucleoside analogue with a ribose lacking both 2' and 3' is called cordycepin, an anticancer drug.

A vast number of nucleobases analogues exist. The most common application are used as fluorescent probes, either directly or indirectly, such as Aminoallyl nucleotide which are used to label cRNA or cDNA in microarrays. Several groups are working on alternative "extra" base pairs to extend the genetic code, such as isoguanine and isocyanine or the fluorescent 2-amino-6-(2-thienyl)purine and pyrrole-2-carbaldehyde.

Analogues are chemically synthesised (protection chemistry), a protected nucleotide is a phosphoramidite.

Reference

Kimoto M et al. Fluorescent probing for RNA molecules by an unnatural base-pair system. Nucleic Acids Res. 2007;35(16):5360-9. Johnson SC et al. A third base pair for the polymerase chain reaction: inserting isoC and isoG. Nucleic Acids Res. 2004 Mar 29;32(6):1937-41.

Molecular biology Genetics Category: Molecular genetics Category: RNA Category: RNA Interference Category: Gene expression