PNA
Encyclopedia
Polymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
similar to DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
or RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
invented by Peter E. Nielsen (Univ. Copenhagen), Michael Egholm (Univ. Copenhagen), Rolf H. Berg (Risø National Lab), and Ole Buchardt (Univ. Copenhagen) in 1991.
DNA and RNA have a deoxyribose
Deoxyribose
Deoxyribose, more, precisely 2-deoxyribose, is a monosaccharide with idealized formula H---3-H. Its name indicates that it is a deoxy sugar, meaning that it is derived from the sugar ribose by loss of an oxygen atom...
and ribose
Ribose
Ribose is an organic compound with the formula C5H10O5; specifically, a monosaccharide with linear form H––4–H, which has all the hydroxyl groups on the same side in the Fischer projection....
sugar backbone, respectively, whereas PNA's backbone is composed of repeating N-(2-aminoethyl)-glycine units linked by peptide bond
Peptide bond
This article is about the peptide link found within biological molecules, such as proteins. A similar article for synthetic molecules is being created...
s. PNA is not known to occur naturally. The various purine
Purine
A purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....
and pyrimidine
Pyrimidine
Pyrimidine is a heterocyclic aromatic organic compound similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring...
bases are linked to the backbone by methylene carbonyl
Carbonyl
In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups....
bonds. PNAs are depicted like peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
s, with the N
Nitrogen
Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...
-terminus at the first (left) position and the C
Carbon
Carbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...
-terminus at the right.
Since the backbone of PNA contains no charged phosphate
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...
groups, the binding between PNA/DNA strands is stronger than between DNA/DNA strands due to the lack of electrostatic repulsion. Unfortunately, this also causes it to be rather hydrophobic, which makes it difficult to deliver to body cells in solution without being flushed out of the body first. Early experiments with homopyrimidine strands (strands consisting of only one repeated pyrimidine
Pyrimidine
Pyrimidine is a heterocyclic aromatic organic compound similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring...
base) have shown that the Tm ("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
Denaturation (biochemistry)
Denaturation is a process in which proteins or nucleic acids lose their tertiary structure and secondary structure by application of some external stress or compound, such as a strong acid or base, a concentrated inorganic salt, an organic solvent , or heat...
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
Antisense therapy
Antisense therapy is a form of treatment for genetic disorders or infections.When the genetic sequence of a particular gene is known to be causative of a particular disease, it is possible to synthesize a strand of nuc acid that will bind to the messenger RNA produced by that gene and inactivate...
. 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 nuclease
Nuclease
A nuclease is an enzyme capable of cleaving the phosphodiester bonds between the nucleotide subunits of nucleic acids. Older publications may use terms such as "polynucleotidase" or "nucleodepolymerase"....
s or protease
Protease
A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....
s, making them resistant to enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
degradation. PNAs are also stable over a wide pH
PH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
range. Though an unmodified PNA cannot readily cross cell membranes to enter the cytosol, covalently coupling a cell penetrating peptide
Cell penetrating peptide
Cell-penetrating peptides are short peptides that facilitate cellular uptake of various molecular cargo . The "cargo" is associated with the peptides either through chemical linkage via covalent bonds or through non-covalent interactions...
to a PNA can improve cytosolic delivery.
It has been hypothesized that the earliest life on Earth
Earth
Earth is the third planet from the Sun, and the densest and fifth-largest of the eight planets in the Solar System. It is also the largest of the Solar System's four terrestrial planets...
may have used PNA as a genetic material due to its extreme robustness, simpler formation and possible spontaneous polymerization
Polymerization
In polymer chemistry, polymerization is a process of reacting monomer molecules together in a chemical reaction to form three-dimensional networks or polymer chains...
at 100°C (while water at standard pressure boils at this temperature, water at high pressure—as in deep ocean—boils at higher temperatures). If this is so, life evolved
Chemical evolution
Chemical evolution may refer to:*Nucleosynthesis, the creation of chemical elements in the universe either through the Big Bang, or supernovae*Abiogenesis, the transition from nonliving elements to living systems...
to a DNA/RNA-based system only at a later stage. Evidence for this PNA world hypothesis is however far from conclusive. See RNA world hypothesis
RNA world hypothesis
The RNA world hypothesis proposes that life based on ribonucleic acid pre-dates the current world of life based on deoxyribonucleic acid , RNA and proteins. RNA is able both to store genetic information, like DNA, and to catalyze chemical reactions, like an enzyme protein...
for related information.
The name is somewhat of a misnomer as PNA is not an acid.
Applications
- Alteration of gene expression - both as inhibitor and promoter in different cases
- Antigene and antisense therapeutic agent
- Anticancer agent
- Antiviral, Antibacterial and Antiparasitic agent
- Molecular tools and probes of biosensor
- Detection of DNA sequences
See also
- Peptide synthesisPeptide synthesisIn organic chemistry, peptide synthesis is the production of peptides, which are organic compounds in which multiple amino acids are linked via amide bonds which are also known as peptide bonds...
- Oligonucleotide synthesisOligonucleotide synthesisOligonucleotide synthesis is the chemical synthesis of relatively short fragments of nucleic acids with defined chemical structure . The technique is extremely useful in current laboratory practice because it provides a rapid and inexpensive access to custom-made oligonucleotides of the desired...
- Glycol nucleic acid
- Threose nucleic acid