Peptide nucleic acid

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PNA monomer.

Peptide nucleic acid (engl. Peptide nucleic acid , PNA , to German also briefly PNS ) is an analogue of the nucleic acids RNA and DNA in which the sugar - phosphate -Rückgrat by a pseudo- peptide is replaced. The backbone often consists of aminoethylglycine units that are connected to one another via neutral amide bonds (instead of the charged phosphodiester bonds in DNA).

structure

PNA polymer.

PNAs are organic polymers that have chemical properties in common with RNA and DNA. There are differences in the basic structure, which in nucleic acids consists of sugar molecules, while PNA has a peptide backbone. The four canonical nucleobases ( adenine , cytosine , guanine and thymine ) are linked to this basic structure . The Nielsen PNA shown on the right uses N - (2-aminoethyl) glycine as the backbone. The secondary amino group is substituted with a nucleobase acetic acid. Alanyl-PNA is another peptide nucleic acid. The alanyl-PNA oligomer consists of a regular peptide strand made up of modified alanyl monomers. The side chains are substituted with the nucleobases at β-positions. By alternating configuration of the amino acid building blocks, a repetitive alanyl peptide strand in a β-sheet conformation can be obtained.

properties

PNAs have a high biological stability because they are neither broken down by nucleases nor by proteases . They also have a higher affinity for complementary DNA or RNA sequences than analog DNA oligomers.

Advantages over DNA oligonucleotides:

  • Higher hybrid stability enables higher and thus more stringent hybridization temperatures.
  • Smaller oligomer lengths lead to higher diffusion rates and thus to faster hybridization kinetics.
  • Salt-independent hybridization allows hybridization at low ionic strengths. Therefore, direct hybridization with PCR amplificates can take place without prior denaturation of the DNA double strands, because PNA, in contrast to DNA or RNA, can still form hybrids under these conditions. Potential secondary structures that have a disruptive effect on hybridization are also dissolved within the target molecules by low ionic strengths.

application

PNA oligomers are in principle suitable for all applications in which synthetic DNA is used. PNAs can be used as potential antigen and antisense therapeutics.

Chemical evolution

see also main article: Chemical evolution

Peptide nucleic acids are discussed as precursors of macromolecules that occur in organisms today. Concepts of chemical evolution that preceded the creation of life are based on the creation of complex molecules from simpler ones through autocatalytic reactions.

Such a model is being developed by representatives of the RNA world hypothesis. However, RNA itself is a complicated molecule, so simpler precursors seem necessary to explain. Stanley Miller and Leslie Orgel suggested that PNA was such a precursor. It has the ability to self-replicate and catalyze chemical reactions, but is more simply structured than RNA.

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 Orgel group did not claim that PNA itself was the origin of life, their work shows that it is possible to develop a more complex molecule from a simpler precursor. Although the formation of PNA under prebiotic conditions has not yet been clarified, KE Nelson and colleagues were able to show in 2000 that the components of PNA can be formed relatively easily under assumed prebiotic conditions.

Individual evidence

  1. ↑ a b Entry on peptide nucleic acid. In: Römpp Online . Georg Thieme Verlag, accessed on December 29, 2014.
  2. ^ Lottspeich, F .; Zorbas, H., ed., Bioanalytik, 2nd ed .; Spectrum: Heidelberg, (2006).
  3. ↑ KE Nelson, M. Levy, SL Miller: Peptide nucleic acids rather than RNA may have been the first genetic molecule. In: Proceedings of the National Academy of Sciences . Volume 97, Number 8, April 2000, ISSN  0027-8424 , pp. 3868-3871, PMID 10760258 , PMC 18108 (free full text).

literature

See also