Peptide nucleic acid

Peptide nucleic acid (English peptide nucleic acid, PNA, and to German short PNS) is an analogue of the nucleic acids, RNA and DNA in which the sugar-phosphate backbone is replaced by a pseudopeptide. The backbone is often from aminoethylglycine units are neutral amide bonds connected to each other (instead of the charged phosphodiester bonds of DNA).

Structure

PNAs are organic polymers having chemical similarities to RNA and DNA. Differences exist in the skeleton, which consists in the nucleic acids from sugar molecules, while the PNA comprises a peptidic backbone. To this basic structure, the four canonical nucleobases (adenine, cytosine, guanine, and thymine ) are connected. The pictured right Nielsen PNA used N-(2 -aminoethyl ) glycine as the backbone. The secondary amino group is substituted with a nucleobase acetic acid. Another peptide nucleic acid, the alanyl- PNA Represents the alanyl- PNA oligomer consists of a regular peptide strand composed of modified alanyl- monomers. The side chains are substituted at β - positions with the nucleobases. By alternating configuration of the amino acid building blocks, a repetitive Alanylpeptidstrang can be obtained in β - sheet conformation.

Properties

PNAs have a high biological stability, since they are not degraded by nucleases or proteases. They also have a higher affinity for complementary DNA or RNA sequences than analogous DNA oligomers.

Advantages over DNA oligonucleotides:

• Higher hybrid stability allows higher and thus more stringent hybridization temperatures.
• Lower oligomer lengths lead to higher diffusion rates and thus faster hybridization kinetics.
• Salt -independent hybridization allows hybridization at low ionic strengths. Therefore, hybridization can be carried out directly with PCR amplicons without prior denaturation of the double stranded DNA, as PNA, in contrast to DNA or RNA under these conditions or can form hybrids. Also, potential secondary structures that could interfere with the hybridization, resolved within the target molecules by low ionic strengths.

Application

PNA oligomers are in principle suitable for all applications where synthetic DNA is inserted. PNAs can be used as a potential antigen and anti-sense therapeutics.

Chemical Evolution

Peptide nucleic acids are discussed as a precursor of macromolecules which occur in today organisms. Notions of chemical evolution that preceded the origin of life, based on the emergence of more complex molecules from simpler ones by autocatalytic reactions.

Such a model is being developed by representatives of the RNA world hypothesis. However, the RNA itself is a complicated molecule, so that simpler precursor to the explanation seem necessary. Stanley Miller and Leslie organ suggested that PNA is such a precursor. She has the ability to replicate itself and catalyze chemical reactions but is simpler than RNA constructed.

Leslie Orgel and his research group at the Salk Institute for Biological Studies in San Diego showed that PNA can serve as a template for their own reproduction and for the formation of RNA. Although the group has not claimed to organ that PNA has been the origin of life itself, shows her work that the development of a more complex molecule from a simpler precursor is possible. Although the formation of PNA is not yet clear under prebiotic conditions, but could KE Nelson et al. show in 2000 that the components can be accepted by PNA form under prebiotic conditions relatively easily.