'Peptide nucleic acid' (PNA) is a chemical similar to
DNA or
RNA. PNA is not known to occur naturally in existing life on Earth but is artificially synthesized and used in some biological research and medical treatments.
DNA and RNA have a
deoxyribose and
ribose sugar backbone, respectively, whereas PNA's backbone is composed of repeating N-(2-aminoethyl)-glycine units linked by
peptide bonds. The various
purine and
pyrimidine bases are linked to the backbone by
methylene carbonyl bonds. PNAs are depicted like
peptides, with the
N-terminus at the first (left) position and the
C-terminus at the right.
Since the backbone of PNA contains no charged
phosphate groups, the binding between PNA/DNA strands is stronger than between DNA/DNA strands due to the lack of electrostatic repulsion. Early experiments with homopyrimidine strands (strands consisting of only one repeated
pyrimidine base) have shown that the T
m ("melting" temperature) of a 6-base thymine PNA/adenine DNA double helix was 31°C in comparison to an equivalent 6-base DNA/DNA duplex that
denatures at a temperature less than 10°C. Mixed base PNA molecules are true mimics of DNA molecules in terms of base-pair recognition. PNA/PNA binding is stronger than PNA/DNA binding.
Synthetic peptide nucleic acid oligomers have been used in recent years in molecular biology procedures, diagnostic assays and
antisense therapies. Due to their higher binding strength it is not necessary to design long PNA oligomers for use in these roles, which usually require oligonucleotide probes of 20-25 bases. The main concern of the length of the PNA-oligomers is to guarantee the specificity. PNA oligomers also show greater specificity in binding to complementary DNAs, with a PNA/DNA base mismatch being more destabilizing than a similar mismatch in a DNA/DNA duplex. This binding strength and specificity also applies to PNA/RNA duplexes. PNAs are not easily recognized by either
nucleases or
proteases, making them resistant to
enzyme degradation. PNAs are also stable over a wide
pH range.
It has been hypothesized that the earliest life on
Earth may have used PNA as a genetic material due to its extreme robustness, simpler formation and possible spontaneous
polymerization at 100°C (while water at standard pressure boils at this temperature, water at high pressure - as in deep ocean - boil at higher temperatures). If this is so, life transitioned to a DNA/RNA-based system only at a later stage
[1]
[2]. Evidence for this hypothesis is however far from conclusive. See
RNA world hypothesis for related information.
References
1. Nelson, K.E., Levy, M., and Miller, S.L. Peptide nucleic acids rather than RNA may have been the first genetic molecule (2000) Proc. Natl. Acad. Sci. USA 97, 3868–3871.
2. Alberts, Johnson, Lewis, Raff, Roberts and Walter, ''Molecular Biology of the Cell'', 4th Edition, Routledge, March, 2002, ISBN 0-8153-3218-1.
External links
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An overview of the PNA molecule
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Recognition of chromosomal DNA by PNAs
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Alternative Nucleic Acid Analogues for Programmable Assembly: Hybridization of LNA to PNA
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The peptide nucleic acids (PNAs): a new generation of probes for genetic and cytogenetic analyses
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A New Game of Life