Peptide nucleic acid

Peptide nucleic acid (PNA) is an artificially synthesized polymer similar to DNA or RNA.^[1]

Synthetic peptide nucleic acid oligomers have been used in recent years in molecular biology procedures, diagnostic assays, and antisense therapies.^[2] 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 degradation by enzymes. PNAs are also stable over a wide pH range. Though an unmodified PNA cannot readily cross the cell membrane to enter the cytosol, covalent coupling of a cell penetrating peptide to a PNA can improve cytosolic delivery.^[3]

PNA is not known to occur naturally but N-(2-aminoethyl)-glycine (AEG), the backbone of PNA, has been hypothesized to be an early form of genetic molecule for life on Earth and is produced by cyanobacteria and is a neurotoxin.^[4]

PNA was invented by Peter E. Nielsen (Univ. Copenhagen), Michael Egholm (Univ. Copenhagen), Rolf H. Berg (Risø National Lab), and Ole Buchardt (Univ. Copenhagen) in 1991.^[1]

^ ^a ^b Nielsen PE, Egholm M, Berg RH, Buchardt O (December 1991). "Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide". Science. 254 (5037): 1497–500. Bibcode:1991Sci...254.1497N. doi:10.1126/science.1962210. PMID 1962210.
^ Gupta A, Mishra A, Puri N (October 2017). "Peptide nucleic acids: Advanced tools for biomedical applications". Journal of Biotechnology. 259: 148–159. doi:10.1016/j.jbiotec.2017.07.026. PMC 7114329. PMID 28764969.
^ Zhao XL, Chen BC, Han JC, Wei L, Pan XB (November 2015). "Delivery of cell-penetrating peptide-peptide nucleic acid conjugates by assembly on an oligonucleotide scaffold". Scientific Reports. 5: 17640. Bibcode:2015NatSR...517640Z. doi:10.1038/srep17640. PMC 4661726. PMID 26612536.
^ Banack SA, Metcalf JS, Jiang L, Craighead D, Ilag LL, Cox PA (7 November 2012). "Cyanobacteria Produce N-(2-Aminoethyl)Glycine, a Backbone for Peptide Nucleic Acids Which May Have Been the First Genetic Molecules for Life on Earth". PLOS ONE. 7 (11): e49043. doi:10.1371/journal.pone.0049043. PMC 3492184. PMID 23145061.

[Nielsen_1991-1] Nielsen PE, Egholm M, Berg RH, Buchardt O (December 1991). "Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide". Science. 254 (5037): 1497–500. Bibcode:1991Sci...254.1497N. doi:10.1126/science.1962210. PMID 1962210.

[2] Gupta A, Mishra A, Puri N (October 2017). "Peptide nucleic acids: Advanced tools for biomedical applications". Journal of Biotechnology. 259: 148–159. doi:10.1016/j.jbiotec.2017.07.026. PMC 7114329. PMID 28764969.

[3] Zhao XL, Chen BC, Han JC, Wei L, Pan XB (November 2015). "Delivery of cell-penetrating peptide-peptide nucleic acid conjugates by assembly on an oligonucleotide scaffold". Scientific Reports. 5: 17640. Bibcode:2015NatSR...517640Z. doi:10.1038/srep17640. PMC 4661726. PMID 26612536.

[4] Banack SA, Metcalf JS, Jiang L, Craighead D, Ilag LL, Cox PA (7 November 2012). "Cyanobacteria Produce N-(2-Aminoethyl)Glycine, a Backbone for Peptide Nucleic Acids Which May Have Been the First Genetic Molecules for Life on Earth". PLOS ONE. 7 (11): e49043. doi:10.1371/journal.pone.0049043. PMC 3492184. PMID 23145061.

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