1.
Base pair
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A base pair is a unit consisting of two nucleobases bound to each other by hydrogen bonds. They form the blocks of the DNA double helix. Dictated by specific hydrogen bonding patterns, Watson-Crick base pairs allow the DNA helix to maintain a regular helical structure that is dependent on its nucleotide sequence. The complementary nature of this structure provides a backup copy of all genetic information encoded within double-stranded DNA. Many DNA-binding proteins can recognize specific base pairing patterns that identify particular regulatory regions of genes, intramolecular base pairs can occur within single-stranded nucleic acids. The size of a gene or an organisms entire genome is often measured in base pairs because DNA is usually double-stranded. Hence, the number of base pairs is equal to the number of nucleotides in one of the strands. The haploid human genome is estimated to be about 3.2 billion bases long and to contain 20, a kilobase is a unit of measurement in molecular biology equal to 1000 base pairs of DNA or RNA. The total amount of related DNA base pairs on Earth is estimated at 5.0 x 1037, in comparison, the total mass of the biosphere has been estimated to be as much as 4 TtC. Hydrogen bonding is the interaction that underlies the base-pairing rules described above. Appropriate geometrical correspondence of hydrogen donors and acceptors allows only the right pairs to form stably. Purine-pyrimidine base pairing of AT or GC or UA results in proper duplex structure, the only other purine-pyrimidine pairings would be AC and GT and UG, these pairings are mismatches because the patterns of hydrogen donors and acceptors do not correspond. The GU pairing, with two bonds, does occur fairly often in RNA. Higher GC content results in higher melting temperatures, it is, therefore, on the converse, regions of a genome that need to separate frequently — for example, the promoter regions for often-transcribed genes — are comparatively GC-poor. GC content and melting temperature must also be taken into account when designing primers for PCR reactions, the following DNA sequences illustrate pair double-stranded patterns. By convention, the top strand is written from the 5 end to the 3 end, thus and this is due to their isosteric chemistry. One common mutagenic base analog is 5-bromouracil, which resembles thymine, most intercalators are large polyaromatic compounds and are known or suspected carcinogens. Examples include ethidium bromide and acridine, an unnatural base pair is a designed subunit of DNA which is created in a laboratory and does not occur in nature
2.
Hydrogen bond
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Hydrogen bonds can occur between molecules or within different parts of a single molecule. Depending on geometry and environment, the hydrogen bond free energy content is between 1 and 5 kcal/mol and this makes it stronger than a van der Waals interaction, but weaker than covalent or ionic bonds. This type of bond can occur in molecules such as water and in organic molecules like DNA. Intermolecular hydrogen bonding is responsible for the boiling point of water compared to the other group 16 hydrides that have much weaker hydrogen bonds. Intramolecular hydrogen bonding is responsible for the secondary and tertiary structures of proteins. It also plays an important role in the structure of polymers, in 2011, an IUPAC Task Group recommended a modern evidence-based definition of hydrogen bonding, which was published in the IUPAC journal Pure and Applied Chemistry. An accompanying detailed technical report provides the rationale behind the new definition, a hydrogen atom attached to a relatively electronegative atom will play the role of the hydrogen bond donor. This electronegative atom is usually fluorine, oxygen, or nitrogen, a hydrogen attached to carbon can also participate in hydrogen bonding when the carbon atom is bound to electronegative atoms, as is the case in chloroform, CHCl3. An example of a hydrogen donor is the hydrogen from the hydroxyl group of ethanol. In a hydrogen bond, the electronegative atom not covalently attached to the hydrogen is named proton acceptor, because of the small size of hydrogen relative to other atoms and molecules, the resulting charge, though only partial, represents a large charge density. A hydrogen bond results when this positive charge density attracts a lone pair of electrons on another heteroatom. The hydrogen bond is described as an electrostatic dipole-dipole interaction. These covalent features are more substantial when acceptors bind hydrogens from more electronegative donors, the partially covalent nature of a hydrogen bond raises the following questions, To which molecule or atom does the hydrogen nucleus belong. And Which should be labeled donor and which acceptor, liquids that display hydrogen bonding are called associated liquids. Hydrogen bonds can vary in strength from weak to extremely strong. For example, the central interresidue N−H···N hydrogen bond between guanine and cytosine is much stronger in comparison to the N−H···N bond between the adenine-thymine pair, the length of hydrogen bonds depends on bond strength, temperature, and pressure. The bond strength itself is dependent on temperature, pressure, bond angle, the typical length of a hydrogen bond in water is 197 pm. The ideal bond angle depends on the nature of the hydrogen bond donor, moore and Winmill used the hydrogen bond to account for the fact that trimethylammonium hydroxide is a weaker base than tetramethylammonium hydroxide
3.
Nucleoside
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Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase and a sugar, whereas a nucleotide is composed of a nucleobase, a five-carbon sugar. In a nucleoside, the base is bound to either ribose or deoxyribose via a beta-glycosidic linkage, examples of nucleosides include cytidine, uridine, adenosine, guanosine, thymidine and inosine. While a nucleoside is a linked to a sugar, a nucleotide is composed of a nucleoside. Thus, nucleosides can be phosphorylated by specific kinases in the cell on the primary alcohol group to produce nucleotides. Nucleotides are the molecular building-blocks of DNA and RNA, the nucleosides, in turn, are subsequently broken down, in the lumen of the digestive system by nucleosidases into nucleobases and ribose or deoxyribose. In addition, nucleotides can be broken down, inside the cell into nitrogenous bases, in medicine several nucleoside analogues are used as antiviral or anticancer agents. The viral polymerase incorporates these compounds with non-canonical bases and these compounds are activated in the cells by being converted into nucleotides. They are administered as nucleosides since charged nucleotides cannot easily cross cell membranes, in molecular biology, several analogues of the sugar backbone exist. Due to the low stability of RNA, which is prone to hydrolysis and this is achieved by using a different backbone sugar. These analogues include LNA, morpholino, PNA and these nucleotides possess the non-canonical sugar dideoxyribose, which lacks 3 hydroxyl group. It therefore cannot bond with the base and terminates the chain. Arabinosyl nucleosides Nucleobase Synthesis of nucleosides
4.
Nucleotide
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Nucleotides are organic molecules that serve as the monomer units for forming the nucleic acid polymers DNA and RNA, both of which are essential biomolecules in all life-forms on Earth. Nucleotides are the blocks of nucleic acids, they are composed of three subunit molecules, a nitrogenous base, a five-carbon sugar, and at least one phosphate group. They are also known as phosphate nucleotides, a nucleoside is a nitrogenuous base and a 5-carbon sugar. Thus a nucleoside plus a group yields a nucleotide. Nucleotides also play a role in life-form metabolism at the fundamental. In addition, nucleotides participate in signaling, and are incorporated into important cofactors of enzymatic reactions. In experimental biochemistry, nucleotides can be radiolabeled with radionuclides to yield radionucleotides, a nucleotide is composed of three distinctive chemical sub-units, a five-carbon sugar molecule, a nitrogenous base—which two together are called a nucleoside—and one phosphate group. With all three joined, a nucleotide is also termed a nucleoside monophosphate, thus, the terms nucleoside diphosphate or nucleoside triphosphate may also indicate nucleotides. Nucleotides contain either a purine or a pyrimidine base—i. e, the nitrogenous base molecule, also known as a nucleobase—and are termed ribonucleotides if the sugar is ribose, or deoxyribonucleotides if the sugar is deoxyribose. These chain-joins of sugar and phosphate molecules create a backbone strand for a single- or double helix, in any one strand, the chemical orientation of the chain-joins runs from the 5-end to the 3-end —referring to the five carbon sites on sugar molecules in adjacent nucleotides. Unlike in nucleic acid nucleotides, singular cyclic nucleotides are formed when the group is bound twice to the same sugar molecule. These individual nucleotides function in cell metabolism rather than the nucleic acid structures of long-chain molecules, nucleic acids then are polymeric macromolecules assembled from nucleotides, the monomer-units of nucleic acids. The purine bases adenine and guanine and pyrimidine base cytosine occur in both DNA and RNA, while the pyrimidine bases thymine and uracil in just one, adenine forms a base pair with thymine with two hydrogen bonds, while guanine pairs with cytosine with three hydrogen bonds. Nucleotides can be synthesized by a variety of both in vitro and in vivo. In vivo, nucleotides can be synthesized de novo or recycled through salvage pathways, the components used in de novo nucleotide synthesis are derived from biosynthetic precursors of carbohydrate and amino acid metabolism, and from ammonia and carbon dioxide. The liver is the organ of de novo synthesis of all four nucleotides. De novo synthesis of pyrimidines and purines follows two different pathways, purines, however, are first synthesized from the sugar template onto which the ring synthesis occurs. For reference, the syntheses of the purine and pyrimidine nucleotides are carried out by several enzymes in the cytoplasm of the cell, nucleotides undergo breakdown such that useful parts can be reused in synthesis reactions to create new nucleotides
5.
Nucleic acid
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Nucleic acids are biopolymers, or large biomolecules, essential to all known forms of life. They are composed of monomers, which are made of three components, a 5-carbon sugar, a phosphate group, and a nitrogenous base. If the sugar is a simple ribose, the polymer is RNA, if the sugar is derived from ribose as deoxyribose, Nucleic acids are arguably the most important of all biomolecules. They are found in abundance in all living things, where they function to create and encode, the encoded information is contained and conveyed via the nucleic acid sequence, which provides the ladder-step ordering of nucleotides within the molecules of RNA and DNA. Using amino acids and the known as protein synthesis, the specific sequencing in DNA of these nucleobase-pairs enables storing and transmitting coded instructions as genes. In RNA, base-pair sequencing provides for manufacturing new proteins that determine the frames and parts, Nucleic acids were discovered by Friedrich Miescher in 1869. In 1889 Richard Altmann discovered that nuclein has acidic properties, and it became called nucleic acid In 1938 Astbury, in 1953 Watson and Crick determined the structure of DNA. The term nucleic acid is the name for DNA and RNA, members of a family of biopolymers. Nucleic acids were named for their initial discovery within the nucleus, all living cells contain both DNA and RNA, while viruses contain either DNA or RNA, but usually not both. The basic component of nucleic acids is the nucleotide, each of which contains a pentose sugar, a phosphate group. Nucleic acids are generated within the laboratory, through the use of enzymes. The chemical methods also enable the generation of altered nucleic acids that are not found in nature, Nucleic acids are generally very large molecules. Indeed, DNA molecules are probably the largest individual molecules known, well-studied biological nucleic acid molecules range in size from 21 nucleotides to large chromosomes. In most cases, naturally occurring DNA molecules are double-stranded and RNA molecules are single-stranded, Nucleic acids are linear polymers of nucleotides. Each nucleotide consists of three components, a purine or pyrimidine nucleobase, a sugar, and a phosphate group. The substructure consisting of a nucleobase plus sugar is termed a nucleoside, Nucleic acid types differ in the structure of the sugar in their nucleotides–DNA contains 2-deoxyribose while RNA contains ribose. Also, the found in the two nucleic acid types are different, adenine, cytosine, and guanine are found in both RNA and DNA, while thymine occurs in DNA and uracil occurs in RNA. The sugars and phosphates in nucleic acids are connected to other in an alternating chain through phosphodiester linkages
6.
RNA
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Ribonucleic acid is a polymeric molecule essential in various biological roles in coding, decoding, regulation, and expression of genes. RNA and DNA are nucleic acids, and, along with proteins and carbohydrates, like DNA, RNA is assembled as a chain of nucleotides, but unlike DNA it is more often found in nature as a single-strand folded onto itself, rather than a paired double-strand. Cellular organisms use messenger RNA to convey information that directs synthesis of specific proteins. Many viruses encode their genetic information using an RNA genome, some RNA molecules play an active role within cells by catalyzing biological reactions, controlling gene expression, or sensing and communicating responses to cellular signals. One of these processes is protein synthesis, a universal function where RNA molecules direct the assembly of proteins on ribosomes. This process uses transfer RNA molecules to deliver amino acids to the ribosome, analysis of these RNAs has revealed that they are highly structured. Unlike DNA, their structures do not consist of long double helices, in this fashion, RNAs can achieve chemical catalysis. For instance, determination of the structure of the enzyme that catalyzes peptide bond formation—revealed that its active site is composed entirely of RNA. Each nucleotide in RNA contains a sugar, with carbons numbered 1 through 5. A base is attached to the 1 position, in general, adenine, cytosine, guanine, adenine and guanine are purines, cytosine and uracil are pyrimidines. A phosphate group is attached to the 3 position of one ribose, the phosphate groups have a negative charge each, making RNA a charged molecule. The bases form hydrogen bonds between cytosine and guanine, between adenine and uracil and between guanine and uracil, however, other interactions are possible, such as a group of adenine bases binding to each other in a bulge, or the GNRA tetraloop that has a guanine–adenine base-pair. An important structural feature of RNA that distinguishes it from DNA is the presence of a group at the 2 position of the ribose sugar. The A-form geometry results in a deep and narrow major groove. RNA is transcribed with only four bases, but these bases, pseudouridine, in which the linkage between uracil and ribose is changed from a C–N bond to a C–C bond, and ribothymidine are found in various places. Another notable modified base is hypoxanthine, a deaminated adenine base whose nucleoside is called inosine, inosine plays a key role in the wobble hypothesis of the genetic code. The specific roles of many of these modifications in RNA are not fully understood, the functional form of single-stranded RNA molecules, just like proteins, frequently requires a specific tertiary structure. The scaffold for this structure is provided by secondary structural elements that are hydrogen bonds within the molecule and this leads to several recognizable domains of secondary structure like hairpin loops, bulges, and internal loops
7.
DNA
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Deoxyribonucleic acid is a molecule that carries the genetic instructions used in the growth, development, functioning and reproduction of all known living organisms and many viruses. DNA and RNA are nucleic acids, alongside proteins, lipids and complex carbohydrates, most DNA molecules consist of two biopolymer strands coiled around each other to form a double helix. The two DNA strands are termed polynucleotides since they are composed of simpler units called nucleotides. Each nucleotide is composed of one of four nitrogen-containing nucleobases—cytosine, guanine, adenine, or thymine —a sugar called deoxyribose, and a phosphate group. The nucleotides are joined to one another in a chain by covalent bonds between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating sugar-phosphate backbone. The nitrogenous bases of the two polynucleotide strands are bound together, according to base pairing rules, with hydrogen bonds to make double-stranded DNA. The total amount of related DNA base pairs on Earth is estimated at 5.0 x 1037, in comparison the total mass of the biosphere has been estimated to be as much as 4 trillion tons of carbon. The DNA backbone is resistant to cleavage, and both strands of the double-stranded structure store the same biological information and this information is replicated as and when the two strands separate. A large part of DNA is non-coding, meaning that these sections do not serve as patterns for protein sequences, the two strands of DNA run in opposite directions to each other and are thus antiparallel. Attached to each sugar is one of four types of nucleobases and it is the sequence of these four nucleobases along the backbone that encodes biological information. RNA strands are created using DNA strands as a template in a process called transcription, under the genetic code, these RNA strands are translated to specify the sequence of amino acids within proteins in a process called translation. Within eukaryotic cells DNA is organized into structures called chromosomes. During cell division these chromosomes are duplicated in the process of DNA replication, eukaryotic organisms store most of their DNA inside the cell nucleus and some of their DNA in organelles, such as mitochondria or chloroplasts. In contrast prokaryotes store their DNA only in the cytoplasm, within the eukaryotic chromosomes, chromatin proteins such as histones compact and organize DNA. These compact structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed, DNA was first isolated by Friedrich Miescher in 1869. DNA is used by researchers as a tool to explore physical laws and theories, such as the ergodic theorem. The unique material properties of DNA have made it an attractive molecule for material scientists and engineers interested in micro-, among notable advances in this field are DNA origami and DNA-based hybrid materials. DNA is a polymer made from repeating units called nucleotides
8.
Adenine
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It also has functions in protein synthesis and as a chemical component of DNA and RNA. The shape of adenine is complementary to either thymine in DNA or uracil in RNA, the image on the right shows pure adenine, as an independent molecule. When connected into DNA, a covalent bond is formed between deoxyribose sugar and the bottom left nitrogen, so removing the hydrogen, the remaining structure is called an adenine residue, as part of a larger molecule. Adenosine is adenine reacted with ribose as used in RNA and ATP, deoxyadenosine adenine attached to deoxyribose, adenine forms several tautomers, compounds that can be rapidly interconverted and are often considered equivalent. However, in isolated conditions, i. e. in an inert gas matrix and in the gas phase, purine metabolism involves the formation of adenine and guanine. Adenine is one of the two purine nucleobases used in forming nucleotides of the nucleic acids, in DNA, adenine binds to thymine via two hydrogen bonds to assist in stabilizing the nucleic acid structures. In RNA, which is used for synthesis, adenine binds to uracil. Adenine forms adenosine, a nucleoside, when attached to ribose and it forms adenosine triphosphate, a nucleoside triphosphate, when three phosphate groups are added to adenosine. Adenosine triphosphate is used in cellular metabolism as one of the methods of transferring chemical energy between chemical reactions. In older literature, adenine was sometimes called Vitamin B4 and it is no longer considered a true vitamin or part of the Vitamin B complex. However, two B vitamins, niacin and riboflavin, bind with adenine to form the essential cofactors nicotinamide adenine dinucleotide and flavin adenine dinucleotide, hermann Emil Fischer was one of the early scientists to study adenine. It was named in 1885 by Albrecht Kossel, in reference to the pancreas from which Kossels sample had been extracted. On August 8,2011, a report, based on NASA studies with meteorites found on Earth, was published suggesting building blocks of DNA and RNA may have been formed extraterrestrially in outer space
9.
Guanine
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Guanine is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine. In DNA, guanine is paired with cytosine, the guanine nucleoside is called guanosine. With the formula C5H5N5O, guanine is a derivative of purine, being unsaturated, the bicyclic molecule is planar. Guanine, along with adenine and cytosine, is present in both DNA and RNA, whereas thymine is usually only in DNA, and uracil only in RNA. Guanine has two forms, the major keto form and rare enol form. It binds to cytosine through three hydrogen bonds, in cytosine, the amino group acts as the hydrogen bond donor and the C-2 carbonyl and the N-3 amine as the hydrogen-bond acceptors. Guanine has the C-6 carbonyl group that acts as the hydrogen acceptor, while a group at N-1. Guanine can be hydrolyzed with strong acid to glycine, ammonia, carbon dioxide, first, guanine gets deaminated to become xanthine. Guanine oxidizes more readily than adenine, the other purine-derivative base in DNA and its high melting point of 350 °C reflects the intermolecular hydrogen bonding between the oxo and amino groups in the molecules in the crystal. Because of this bonding, guanine is relatively insoluble in water. Between 1882 and 1906, Fischer determined the structure and also showed that uric acid can be converted to guanine, trace amounts of guanine form by the polymerization of ammonium cyanide. These results indicate guanine could arise in frozen regions of the primitive earth. In 1984, Yuasa reported a 0. 00017% yield of guanine after the discharge of NH3, CH4, C 2H6. However, it is whether the presence of guanine was not simply a resultant contaminant of the reaction. 10NH3 + 2CH4 + 4C2H6 + 2H2O → 2C5H8N5O + 25H2 A Fischer-Tropsch synthesis can also be used to form guanine, along with adenine, uracil, traubes synthesis involves heating 2,4, 5-triamino-1, 6-dihydro-6-oxypyrimidine with formic acid for several hours. The word guanine derives from the Spanish loanword guano, which itself is from the Quechua word wanu, as the Oxford English Dictionary notes, guanine is A white amorphous substance obtained abundantly from guano, forming a constituent of the excrement of birds. In 1656 in Paris, a Mr. Jaquin extracted from the scales of the fish Alburnus alburnus so-called pearl essence, in the cosmetics industry, crystalline guanine is used as an additive to various products, where it provides a pearly iridescent effect. It is also used in paints and simulated pearls and plastics
10.
Uracil
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Uracil /ˈjʊərəsɪl/ is one of the four nucleobases in the nucleic acid of RNA that are represented by the letters A, G, C and U. The others are adenine, cytosine, and guanine, in RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced by thymine, Uracil is a demethylated form of thymine. Uracil is a common and naturally occurring pyrimidine derivative, the name uracil was coined in 1885 by the German chemist Robert Behrend, who was attempting to synthesize derivatives of uric acid. Originally discovered in 1900 by Alberto Ascoli, it was isolated by hydrolysis of yeast nuclein, it was found in bovine thymus and spleen, herring sperm. It is a planar, unsaturated compound that has the ability to absorb light, based on 12C/13C isotopic ratios of organic compounds found in the Murchison meteorite, it is believed that uracil, xanthine and related molecules can also be formed extraterrestrially. In 2012, an analysis of data from the Cassini mission orbiting in the Saturn system showed that Titans surface composition may include uracil, in RNA, uracil base-pairs with adenine and replaces thymine during DNA transcription. In DNA, the substitution of thymine for uracil may have increased DNA stability. Uracil pairs with adenine through hydrogen bonding, when base pairing with adenine, uracil acts as both a hydrogen bond acceptor and a hydrogen bond donor. In RNA, uracil binds with a sugar to form the ribonucleoside uridine. When a phosphate attaches to uridine, uridine 5-monophosphate is produced, Uracil undergoes amide-imidic acid tautomeric shifts because any nuclear instability the molecule may have from the lack of formal aromaticity is compensated by the cyclic-amidic stability. The amide tautomer is referred to as the structure, while the imidic acid tautomer is referred to as the lactim structure. These tautomeric forms are predominant at pH7, the lactam structure is the most common form of uracil. Uracil also recycles itself to form nucleotides by undergoing a series of phosphoribosyltransferase reactions, degradation of uracil produces the substrates aspartate, carbon dioxide, and ammonia. C4H4N2O2 → H3NCH2CH2COO− + NH4+ + CO2 Oxidative degradation of uracil produces urea and maleic acid in the presence of H2O2 and Fe2+ or in the presence of diatomic oxygen, the first site of ionization of uracil is not known. The negative charge is placed on the anion and produces a pKa of less than or equal to 12. The basic pKa = -3.4, while the acidic pKa =9.389, in the gas phase, uracil has 4 sites that are more acidic than water. Uracil is rarely found in DNA, and this may have been a change to increase genetic stability
11.
Genetic code
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The genetic code is the set of rules by which information encoded within genetic material is translated into proteins by living cells. Translation is accomplished by the ribosome, which links amino acids in an order specified by mRNA, using transfer RNA molecules to carry amino acids, the genetic code is highly similar among all organisms and can be expressed in a simple table with 64 entries. The code defines how sequences of nucleotide triplets, called codons, with some exceptions, a three-nucleotide codon in a nucleic acid sequence specifies a single amino acid. The vast majority of genes are encoded with a single scheme and that scheme is often referred to as the canonical or standard genetic code, or simply the genetic code, though variant codes exist. While the genetic code determines a proteins amino acid sequence, other genomic regions determine when, efforts to understand how proteins are encoded began after DNAs structure was discovered in 1953. George Gamow postulated that sets of three bases must be employed to encode the 20 standard amino acids used by living cells to build proteins, the Crick, Brenner et al. experiment first demonstrated that codons consist of three DNA bases. Marshall Nirenberg and Heinrich J. Matthaei were the first to reveal the nature of a codon in 1961 and they used a cell-free system to translate a poly-uracil RNA sequence and discovered that the polypeptide that they had synthesized consisted of only the amino acid phenylalanine. They thereby deduced that the codon UUU specified the amino acid phenylalanine, therefore, the codon AAA specified the amino acid lysine, and the codon CCC specified the amino acid proline. Using various copolymers most of the remaining codons were then determined, subsequent work by Har Gobind Khorana identified the rest of the genetic code. Shortly thereafter, Robert W. Holley determined the structure of transfer RNA and this work was based upon Ochoas earlier studies, yielding the latter the Nobel Prize in Physiology or Medicine in 1959 for work on the enzymology of RNA synthesis. Extending this work, Nirenberg and Philip Leder revealed the triplet nature. In these experiments, various combinations of mRNA were passed through a filter that contained ribosomes, unique triplets promoted the binding of specific tRNAs to the ribosome. Leder and Nirenberg were able to determine the sequences of 54 out of 64 codons in their experiments, Khorana, Holley and Nirenberg received the 1968 Nobel for their work. The three stop codons were named by discoverers Richard Epstein and Charles Steinberg, amber was named after their friend Harris Bernstein, whose last name means amber in German. The other two stop codons were named ochre and opal in order to keep the color names theme, H. Murakami and M. Sisido extended some codons to have four and five bases. Steven A. Benner constructed a functional 65th codon, in 2016 the first stable semisynthetic organism was created. It was a bacterium with two synthetic bases, in 2017 a mouse engineered with an extended genetic code that can produce proteins with unnatural amino acids was reported. A codon is defined by the initial nucleotide from which starts and sets the frame for a run of successive triplets
12.
Methyl group
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A methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms — CH3. In formulas, the group is often abbreviated Me, such hydrocarbon groups occur in many organic compounds. It is a stable group in most molecules. While the methyl group is part of a larger molecule. The anion has eight electrons, the radical seven and the cation six. All three forms are highly reactive and rarely observed, the methylium cation exists in the gas phase, but is otherwise not encountered. Some compounds are considered to be sources of the CH3+ cation, the methanide anion exists only in rarefied gas phase or under exotic conditions. It can be produced by electrical discharge in ketene at low pressure, such reagents are generally prepared from the methyl halides, M + CH3X → MCH3 where M is an alkali metal. The methyl radical has the formula CH3 and it exists in dilute gases, but in more concentrated form it readily dimerizes to ethane. It can be produced by decomposition of only certain compounds. The reactivity of a methyl group depends on the adjacent substituents, methyl groups can be quite unreactive. For example, in compounds, the methyl group resists attack by even the strongest acids. The oxidation of a group occurs widely in nature and industry. The oxidation products derived from methyl are CH2OH, CHO, for example, permanganate often converts a methyl group to a carboxyl group, e. g. the conversion of toluene to benzoic acid. Ultimately oxidation of methyl groups gives protons and carbon dioxide, as seen in combustion, demethylation is a common process, and reagents that undergo this reaction are called methylating agents. Common methylating agents are dimethyl sulfate, methyl iodide, and methyl triflate, methanogenesis, the source of natural gas, arises via a demethylation reaction. Certain methyl groups can be deprotonated, for example, the acidity of the methyl groups in acetone is about 1020 more acidic than methane. The resulting carbanions are key intermediates in many reactions in organic synthesis and biosynthesis, fatty acids are produced in this way
13.
Helix
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A helix is a type of smooth space curve, i. e. a curve in three-dimensional space. It has the property that the tangent line at any point makes a constant angle with a line called the axis. Examples of helices are coil springs and the handrails of spiral staircases, a filled-in helix – for example, a spiral ramp – is called a helicoid. Helices are important in biology, as the DNA molecule is formed as two intertwined helices, and many proteins have helical substructures, known as alpha helices, the word helix comes from the Greek word ἕλιξ, twisted, curved. Helices can be either right-handed or left-handed, handedness is a property of the helix, not of the perspective, a right-handed helix cannot be turned to look like a left-handed one unless it is viewed in a mirror, and vice versa. Most hardware screw threads are right-handed helices, the alpha helix in biology as well as the A and B forms of DNA are also right-handed helices. The Z form of DNA is left-handed, the pitch of a helix is the height of one complete helix turn, measured parallel to the axis of the helix. A double helix consists of two helices with the axis, differing by a translation along the axis. A conic helix may be defined as a spiral on a conic surface, an example is the Corkscrew roller coaster at Cedar Point amusement park. A circular helix, has constant band curvature and constant torsion, a curve is called a general helix or cylindrical helix if its tangent makes a constant angle with a fixed line in space. A curve is a general helix if and only if the ratio of curvature to torsion is constant, a curve is called a slant helix if its principal normal makes a constant angle with a fixed line in space. It can be constructed by applying a transformation to the frame of a general helix. Some curves found in nature consist of multiple helices of different handedness joined together by transitions known as tendril perversions, in mathematics, a helix is a curve in 3-dimensional space. The following parametrisation in Cartesian coordinates defines a particular helix, Probably the simplest equations for one is x = cos , y = sin , z = t. As the parameter t increases, the point traces a right-handed helix of pitch 2θ and radius 1 about the z-axis, in cylindrical coordinates, the same helix is parametrised by, r =1, θ = t, h = t. A circular helix of radius a and slope b/a is described by the following parametrisation, another way of mathematically constructing a helix is to plot the complex-valued function exi as a function of the real number x. The value of x and the real and imaginary parts of the function value give this plot three real dimensions, except for rotations, translations, and changes of scale, all right-handed helices are equivalent to the helix defined above. The equivalent left-handed helix can be constructed in a number of ways, in music, pitch space is often modeled with helices or double helices, most often extending out of a circle such as the circle of fifths, so as to represent octave equivalency
14.
Complementarity (molecular biology)
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In molecular biology, complementarity describes a relationship between two structures each following the lock-and-key principle. This complementary base pairing allows cells to copy information from one generation to another and even find, the degree of complementarity between two nucleic acid strands may vary, from complete complementarity to no complementarity and determines the stability of the sequences to be together. Furthermore, various DNA repair functions as well as functions are based on base pair complementarity. In biotechnology, the principle of base pair complementarity allows the generation of DNA hybrids between RNA and DNA, and opens the door to modern tools such as cDNA libraries, complementarity is achieved by distinct interactions between nucleobases, adenine, thymine, guanine and cytosine. Adenine and guanine are purines, while thymine, cytosine and uracil are pyrimidines, both types of molecules complement each other and can only base pair with the opposing type of nucleobase. In nucleic acid, nucleobases are held together by hydrogen bonding, the base complement A=T shares two hydrogen bonds, while the base pair G≡C has three hydrogen bonds. All other configurations between nucleobases would hinder double helix formation, DNA strands are oriented in opposite directions, they are said to be antiparallel. A complementary strand of DNA or RNA may be constructed based on nucleobase complementarity, each base pair, A=T vs. G≡C, takes up roughly the same space, thereby enabling a twisted DNA double helix formation without any spatial distortions. Hydrogen bonding between the nucleobases also stabilizes the DNA double helix, complementarity of DNA strands in a double helix make it possible to use one strand as a template to construct the other. This principle plays an important role in DNA replication, setting the foundation of heredity by explaining how genetic information can be passed down to the next generation, complementarity is also utilized in DNA transcription, which generates an RNA strand from a DNA template. DNA repair mechanisms such as proof reading are complementarity based and allow for error correction during DNA replication by removing mismatched nucleobases, nucleic acids strands may also form hybrids in which single stranded DNA may readily anneal with complementary DNA or RNA. This principle is the basis of commonly performed laboratory techniques such as the chain reaction. Two strands of complementary sequence are referred to as sense and anti-sense, the sense strand is, generally, the transcribed sequence of DNA or the RNA that was generated in transcription. While the anti-sense strand is the strand that is complementary to the sense sequence, self-complementarity refers to the fact that a sequence of DNA or RNA may fold back on itself, creating a double-strand like structure. Depending on how close together the parts of the sequence are that are self-complementary, RNA is more likely to form these kinds of structures due to base pair binding not seen in DNA, such as guanine binding with uracil. Complementarity can be found between short nucleic acid stretches and a region or an transcribed gene, and results in base pairing. These short nucleic acid sequences are found in nature and have regulatory functions such as gene silencing. Antisense transcripts are stretches of non coding mRNA that are complementary to the coding sequence, genome wide studies have shown that RNA antisense transcripts occur commonly within nature
15.
Amine
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In organic chemistry, amines are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group, important amines include amino acids, biogenic amines, trimethylamine, and aniline, see Category, Amines for a list of amines. Inorganic derivatives of ammonia are also called amines, such as chloramine, see Category, compounds with a nitrogen atom attached to a carbonyl group, thus having the structure R–CO–NR′R″, are called amides and have different chemical properties from amines. An aliphatic amine has no aromatic ring attached directly to the nitrogen atom, aromatic amines have the nitrogen atom connected to an aromatic ring as in the various anilines. The aromatic ring decreases the alkalinity of the amine, depending on its substituents, the presence of an amine group strongly increases the reactivity of the aromatic ring, due to an electron-donating effect. Amines are organized into four subcategories, Primary amines — Primary amines arise when one of three atoms in ammonia is replaced by an alkyl or aromatic. Important primary alkyl amines include, methylamine, most amino acids, Secondary amines — Secondary amines have two organic substituents bound to the nitrogen together with one hydrogen. Important representatives include dimethylamine, while an example of an aromatic amine would be diphenylamine, tertiary amines — In tertiary amines, nitrogen has three organic substituents. Examples include trimethylamine, which has a fishy smell. Cyclic amines — Cyclic amines are either secondary or tertiary amines, examples of cyclic amines include the 3-membered ring aziridine and the six-membered ring piperidine. N-methylpiperidine and N-phenylpiperidine are examples of tertiary amines. It is also possible to have four organic substituents on the nitrogen and these species are not amines but are quaternary ammonium cations and have a charged nitrogen center. Quaternary ammonium salts exist with many kinds of anions, Amines are named in several ways. Typically, the compound is given the prefix amino- or the suffix, the prefix N- shows substitution on the nitrogen atom. An organic compound with multiple amino groups is called a diamine, triamine, tetraamine, systematic names for some common amines, Hydrogen bonding significantly influences the properties of primary and secondary amines. Thus the melting point and boiling point of amines is higher than those of the corresponding phosphines, for example, methyl and ethyl amines are gases under standard conditions, whereas the corresponding methyl and ethyl alcohols are liquids. Amines possess a characteristic smell, liquid amines have a distinctive fishy smell. The nitrogen atom features a lone pair that can bind H+ to form an ammonium ion R3NH+
16.
Carbonyl group
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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 compounds, as part of many larger functional groups. A compound containing a group is often referred to as a carbonyl compound. The term carbonyl can also refer to carbon monoxide as a ligand in an inorganic or organometallic complex, the remainder of this article concerns itself with the organic chemistry definition of carbonyl, where carbon and oxygen share a double bond. A carbonyl group characterizes the types of compounds, Note that the most specific labels are usually employed. For example, ROR structures are known as acid anhydride rather than the more generic ester, other organic carbonyls are urea and the carbamates, the derivatives of acyl chlorides chloroformates and phosgene, carbonate esters, thioesters, lactones, lactams, hydroxamates, and isocyanates. Examples of inorganic compounds are carbon dioxide and carbonyl sulfide. A special group of compounds are 1, 3-dicarbonyl compounds that have acidic protons in the central methylene unit. Examples are Meldrums acid, diethyl malonate and acetylacetone, because oxygen is more electronegative than carbon, carbonyl compounds often have resonance structures which affect their reactivity. This relative electronegativity draws electron density away from carbon, increasing the bonds polarity, carbon can then be attacked by nucleophiles or a negatively charged part of another molecule. During the reaction, the double bond is broken. This reaction is known as addition-elimination or condensation, the electronegative oxygen also can react with an electrophile, for example a proton in an acidic solution or with Lewis acids to form an oxocarbenium ion. The polarity of oxygen also makes the alpha hydrogens of carbonyl compounds much more acidic than typical sp3 C-H bonds, for example, the pKa values of acetaldehyde and acetone are 16.7 and 19 respectively, while the pKa value of methane is extrapolated to be approximately 50. This is because a carbonyl is in resonance with an enol. The deprotonation of the enol with a base produces an enolate. Amides are the most stable of the carbonyl couplings due to their high resonance stabilization between the nitrogen-carbon and carbon-oxygen bonds, carbonyl groups can be reduced by reaction with hydride reagents such as NaBH4 and LiAlH4, with bakers yeast, or by catalytic hydrogenation. Ketones give secondary alcohols while aldehydes, esters and carboxylic acids give primary alcohols, carbonyls can be alkylated in nucleophilic addition reactions using organometallic compounds such as organolithium reagents, Grignard reagents, or acetylides. Carbonyls also may be alkylated by enolates as in aldol reactions, carbonyls are also the prototypical groups with vinylogous reactivity
17.
Xanthine
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Xanthine, is a purine base found in most human body tissues and fluids and in other organisms. A number of stimulants are derived from xanthine, including caffeine and theobromine, xanthine is a product on the pathway of purine degradation. It is created from guanine by guanine deaminase and it is created from hypoxanthine by xanthine oxidoreductase. It is also created from xanthosine by purine nucleoside phosphorylase, xanthine is subsequently converted to uric acid by the action of the xanthine oxidase enzyme. People with the genetic disorder xanthinuria lack sufficient xanthine oxidase. Derivatives of xanthine are a group of alkaloids commonly used for their effects as mild stimulants and as bronchodilators and they also stimulate the respiratory centre, and are used for treatment of infantile apnea. Due to widespread effects, the range of xanthines is narrow. The therapeutic level is 10-20 micrograms/mL blood, signs of toxicity include tremor, nausea, nervousness, in high doses they can lead to convulsions that are resistant to anticonvulsants. Methylxanthines induce acid and pepsin secretions in the GI tract, methylxanthines are metabolized by cytochrome P450 in the liver. Xanthines are also very rarely as constituents of nucleic acids. Non-specific LC-MS UV Spectroscopy Fourier transform infrared spectrometry Murchison meteorite Xanthene Xanthydrol Xanthone Theobromine poisoning DMPX
18.
Directionality (molecular biology)
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Directionality, in molecular biology and biochemistry, is the end-to-end chemical orientation of a single strand of nucleic acid. In a DNA double helix, the run in opposite directions to permit base pairing between them, which is essential for replication or transcription of the encoded information. The relative positions of structures along a strand of nucleic acid, including genes, directionality is related to, but independent from sense. The other strand is not copied directly, but necessarily its sequence will be similar to that of the RNA, transcription initiation sites generally occur on both strands of an organisms DNA, and specify the location, direction, and circumstances under which transcription will occur. For example, in a typical gene a start codon is a DNA sequence within the sense strand, transcription begins at an upstream site, and as it proceeds through the region it copies the 3′-TAC-5′ from the template strand to produce 5′-AUG-3′ within a messenger RNA. The mRNA is scanned by the ribosome from the 5′ end, by convention, single strands of DNA and RNA sequences are written in a 5′-to-3′ direction except as needed to illustrate the pattern of base pairing. The 5′-end designates the end of the DNA or RNA strand that has the carbon in the sugar-ring of the deoxyribose or ribose at its terminus. A phosphate group attached to the 5′-end permits ligation of two nucleotides, i. e. the covalent binding of a 5′-phosphate to the 3′-hydroxyl group of another nucleotide, removal of the 5′-phosphate prevents ligation. To prevent unwanted nucleic acid ligation, molecular biologists commonly remove the 5′-phosphate with a phosphatase, the 5′-end of nascent messenger RNA is the site at which post-transcriptional capping occurs, a process which is vital to producing mature messenger RNA. Capping increases the stability of the messenger RNA while it undergoes translation and it consists of a methylated nucleotide attached to the messenger RNA in a rare 5′- to 5′-triphosphate linkage. The 5′-flanking region of a gene often denotes a region of DNA which is not transcribed into RNA, the 5′-flanking region contains the gene promoter, and may also contain enhancers or other protein binding sites. The 5′-untranslated region is a region of a gene which is transcribed into mRNA and this region of an mRNA may or may not be translated, but is usually involved in the regulation of translation. The 5′-untranslated region is the portion of the DNA starting from the cap site and this region may have sequences, such as the ribosome binding site and Kozak sequence, which determine the translation efficiency of the mRNA, or which may affect the stability of the mRNA. The 3′-end of a strand is so named due to it terminating at the group of the third carbon in the sugar-ring. The 3′-hydroxyl is necessary in the synthesis of new nucleic acid molecules as it is ligated to the 5′-phosphate of a separate nucleotide, molecular biologists can use nucleotides that lack a 3′-hydroxyl to interrupt the replication of DNA. This technique is known as the dideoxy chain-termination termination method or the Sanger method, the 3′-end of nascent messenger RNA is the site of post-transcriptional polyadenylation, which attaches a chain of 50 to 250 adenosine residues to produce mature messenger RNA. This chain helps in determining how long the messenger RNA lasts in the cell, the 3′-flanking region is a region of DNA that is not copied into the mature mRNA, but which is present adjacent to 3′-end of the gene. The 3′-flanking region often contains sequences that affect the formation of the 3′-end of the message and it may also contain enhancers or other sites to which proteins may bind
19.
Biomolecule
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A more general name for this class of material is biological materials. Biomolecules are usually endogenous but may also be exogenous, for example, pharmaceutical drugs may be natural products or semisynthetic or they may be totally synthetic. Biology and its subsets of biochemistry and molecular biology study biomolecules, most biomolecules are organic compounds, and just four elements—oxygen, carbon, hydrogen, and nitrogen—make up 96% of the human bodys mass. But many other elements, such as the various biometals, are present in small amounts, examples of these include cytidine, uridine, adenosine, guanosine, thymidine and inosine. Nucleosides can be phosphorylated by specific kinases in the cell, producing nucleotides, both DNA and RNA are polymers, consisting of long, linear molecules assembled by polymerase enzymes from repeating structural units, or monomers, of mononucleotides. DNA uses the deoxynucleotides C, G, A, and T, while RNA uses the ribonucleotides C, G, A, modified bases are fairly common, as found in ribosomal RNA or transfer RNAs or for discriminating the new from old strands of DNA after replication. Each nucleotide is made of a nitrogenous base, a pentose. They contain carbon, nitrogen, oxygen, hydrogen and phosphorus and they serve as sources of chemical energy, participate in cellular signaling, and are incorporated into important cofactors of enzymatic reactions. DNA structure is dominated by the double helix formed by Watson-Crick base-pairing of C with G and A with T. This is known as B-form DNA, and is overwhelmingly the most favorable and common state of DNA, its highly specific and stable base-pairing is the basis of reliable genetic information storage. DNA can sometimes occur as single strands or as A-form or Z-form helices, RNA, in contrast, forms large and complex 3D tertiary structures reminiscent of proteins, as well as the loose single strands with locally folded regions that constitute messenger RNA molecules. Those RNA structures contain many stretches of A-form double helix, connected into definite 3D arrangements by single-stranded loops, bulges, examples are tRNA, ribosomes, ribozymes, and riboswitches. Monosaccharides are the simplest form of carbohydrates with only one simple sugar and they essentially contain an aldehyde or ketone group in their structure. The presence of an group in a monosaccharide is indicated by the prefix aldo-. Similarly, a group is denoted by the prefix keto-. Examples of monosaccharides are the hexoses glucose, fructose, and galactose and pentoses, ribose, most saccharides eventually provide fuel for cellular respiration. Disaccharides are formed when two monosaccharides, or two simple sugars, form a bond with removal of water. They can be hydrolyzed to yield their saccharin building blocks by boiling with dilute acid or reacting them with appropriate enzymes, examples of disaccharides include sucrose, maltose, and lactose
20.
Ribose
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Ribose is a carbohydrate with the formula C5H10O5, specifically, it is a pentose monosaccharide with linear form H−−4−H, which has all the hydroxyl groups on the same side in the Fischer projection. The term may refer to either of two enantiomers, the term usually indicates D-ribose, which occurs widely in nature and is discussed here. Its synthetic mirror image, L-ribose, is not found in nature, d-Ribose was first reported in 1891 by Emil Fischer. It is a C-2 carbon epimer of the sugar D-arabinose and ribose itself is named as a rearrangement of letters in the word arabinose. The ribose β-D-ribofuranose forms part of the backbone of RNA and it is related to deoxyribose, which is found in DNA. Phosphorylated derivatives of such as ATP and NADH play central roles in metabolism. CAMP and cGMP, formed from ATP and GTP, serve as messengers in some signalling pathways. Ribose is an aldopentose that, in its open form, has an aldehyde functional group at one end. In the conventional numbering scheme for monosaccharides, the atoms are numbered from C1 to C5. The deoxyribose derivative found in DNA differs from ribose by having a hydrogen atom in place of the group at C2. This hydroxyl group performs a function in RNA splicing, the beta-ribopyranose form predominates in aqueous solution. The “D-” in the name D-ribose refers to the stereochemistry of the carbon atom farthest away from the aldehyde group. In D-ribose, as in all D-sugars, this carbon atom has the configuration as in D-glyceraldehyde. Relative abundance of different forms of ribose in solution, β-D-ribopyranose, α-D-ribopyranose, β-D-ribofuranose, α-D-ribofuranose, in biology, D-ribose must be phosphorylated by the cell before it can be used. Ribokinase catalyzes this reaction by converting D-ribose to D-ribose 5-phosphate, once converted, D-ribose-5-phosphate is available for the manufacturing of the amino acids tryptophan and histidine, or for use in the pentose phosphate pathway. The absorption of D-ribose is 88–100% in the small intestines
21.
Deoxyribose
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Deoxyribose, or more precisely 2-deoxyribose, is a monosaccharide with idealized formula H−−−3−H. Its name indicates that it is a sugar, meaning that it is derived from the sugar ribose by loss of an oxygen atom. Several isomers exist with the formula H−−−3−H, but in all the hydroxyl groups are on the same side in the Fischer projection. The term 2-deoxyribose may refer to either of two enantiomers, the biologically important D-2-deoxyribose and to the rarely encountered mirror image L-2-deoxyribose, D-2-deoxyribose is a precursor to the nucleic acid DNA. 2-deoxyribose is an aldopentose, that is, a monosaccharide with five carbon atoms, as a component of DNA, 2-deoxyribose derivatives have an important role in biology. The DNA molecule, which is the repository of genetic information in life, consists of a long chain of deoxyribose-containing units called nucleotides. In the standard nucleic acid nomenclature, a DNA nucleotide consists of a molecule with an organic base attached to the 1′ ribose carbon. The 5′ hydroxyl of each unit is replaced by a phosphate that is attached to the 3′ carbon of the deoxyribose in the preceding unit. The double-stranded DNA molecules are typically much longer than RNA molecules. The backbone of RNA and DNA are structurally similar, but RNA is single stranded, other biologically important derivatives of deoxyribose include mono-, di-, and triphosphates, as well as 3′-5′ cyclic monophosphates. Deoxyribose is generated from ribose 5-phosphate by enzymes called ribonucleotide reductases and these enzymes catalyse the deoxygenation process. It was discovered in 1929 by Phoebus Levene
22.
DNA replication
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In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. This process occurs in all living organisms and is the basis for biological inheritance, DNA is made up of a double helix of two complementary strands. During replication, these strands are separated, each strand of the original DNA molecule then serves as a template for the production of its counterpart, a process referred to as semiconservative replication. Cellular proofreading and error-checking mechanisms ensure near perfect fidelity for DNA replication, in a cell, DNA replication begins at specific locations, or origins of replication, in the genome. Unwinding of DNA at the origin and synthesis of new results in replication forks growing bi-directionally from the origin. A number of proteins are associated with the fork to help in the initiation and continuation of DNA synthesis. Most prominently, DNA polymerase synthesizes the new strands by adding nucleotides that complement each strand, DNA replication occurs during the S-stage of interphase. DNA replication can also be performed in vitro, DNA polymerases isolated from cells and artificial DNA primers can be used to initiate DNA synthesis at known sequences in a template DNA molecule. The polymerase chain reaction, a laboratory technique, cyclically applies such artificial synthesis to amplify a specific target DNA fragment from a pool of DNA. DNA usually exists as a structure, with both strands coiled together to form the characteristic double-helix. Each single strand of DNA is a chain of four types of nucleotides, nucleotides in DNA contain a deoxyribose sugar, a phosphate, and a nucleobase. These nucleotides form phosphodiester bonds, creating the phosphate-deoxyribose backbone of the DNA double helix with the bases pointing inward. Nucleotides are matched between strands through hydrogen bonds to form base pairs, adenine pairs with thymine, and guanine pairs with cytosine. DNA strands have a directionality, and the different ends of a single strand are called the 3 end and the 5 end. By convention, if the sequence of a single strand of DNA is given. The strands of the helix are anti-parallel with one being 5 to 3. These terms refer to the atom in deoxyribose to which the next phosphate in the chain attaches. Directionality has consequences in DNA synthesis, because DNA polymerase can synthesize DNA in only one direction by adding nucleotides to the 3 end of a DNA strand, the pairing of complementary bases in DNA means that the information contained within each strand is redundant
23.
Transcription (biology)
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Transcription is the first step of gene expression, in which a particular segment of DNA is copied into RNA by the enzyme RNA polymerase. Both DNA and RNA are nucleic acids, which use base pairs of nucleotides as a complementary language, during transcription, a DNA sequence is read by an RNA polymerase, which produces a complementary, antiparallel RNA strand called a primary transcript. Transcription proceeds in the general steps, RNA polymerase, together with one or more general transcription factors. RNA polymerase creates a bubble, which separates the two strands of the DNA helix. This is done by breaking the bonds between complementary DNA nucleotides. RNA sugar-phosphate backbone forms with assistance from RNA polymerase to form an RNA strand, hydrogen bonds of the RNA–DNA helix break, freeing the newly synthesized RNA strand. If the cell has a nucleus, the RNA may be further processed and this may include polyadenylation, capping, and splicing. The RNA may remain in the nucleus or exit to the cytoplasm through the pore complex. The stretch of DNA transcribed into an RNA molecule is called a transcription unit, if the gene encodes a protein, the transcription produces messenger RNA, the mRNA, in turn, serves as a template for the proteins synthesis through translation. Alternatively, the gene may encode for either non-coding RNA, ribosomal RNA, transfer RNA. Overall, RNA helps synthesize, regulate, and process proteins, in virology, the term may also be used when referring to mRNA synthesis from an RNA molecule. For instance, the genome of a negative-sense single-stranded RNA virus may be template for a positive-sense single-stranded RNA and this is because the positive-sense strand contains the information needed to translate the viral proteins for viral replication afterwards. This process is catalyzed by a viral RNA replicase, the regulatory sequence before the coding sequence is called the five prime untranslated region, the sequence after the coding sequence is called the three prime untranslated region. As opposed to DNA replication, transcription results in an RNA complement that includes the nucleotide uracil in all instances where thymine would have occurred in a DNA complement, only one of the two DNA strands serve as a template for transcription. The antisense strand of DNA is read by RNA polymerase from the 3 end to the 5 end during transcription. The complementary RNA is created in the direction, in the 5 →3 direction. This directionality is because RNA polymerase can only add nucleotides to the 3 end of the growing mRNA chain and this use of only the 3 →5 DNA strand eliminates the need for the Okazaki fragments that are seen in DNA replication. This also removes the need for an RNA primer to initiate RNA synthesis, the non-template strand of DNA is called the coding strand, because its sequence is the same as the newly created RNA transcript
24.
Pseudouridine
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Pseudouridine is an isomer of the nucleoside uridine in which the uracil is attached via a carbon-carbon instead of a nitrogen-carbon glycosidic bond. It is the most prevalent of the one hundred different modified nucleosides found in RNA. Ψ is found in all species and in classes of RNA. Ψ is formed by enzymes called Ψ synthases, which post-transcriptionally isomerize specific uridine residues in RNA in a process termed pseudouridylation, currently, about ∼9500 pseudouridine modifications have been identified in mammals and yeast and deposited in RMBase database. It is commonly found in tRNA, associated with thymidine and cytosine in the TΨC arm and is one of the invariant regions of tRNA. The function of it is not very clear, but it is expected to play a role in association with aminoacyl transferases during their interaction with tRNA, recent studies suggest it may offer protection from radiation
25.
Inosine
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Inosine is a nucleoside that is formed when hypoxanthine is attached to a ribose ring via a β-N9-glycosidic bond. Inosine is commonly found in tRNAs and is essential for translation of the genetic code in wobble base pairs. Knowledge of inosine metabolism has led to advances in immunotherapy in recent decades, Inosine monophosphate is oxidised by the enzyme inosine monophosphate dehydrogenase, yielding xanthosine monophosphate, a key precursor in purine metabolism. Mycophenolate mofetil is an anti-metabolite, anti-proliferative drug that acts as an inhibitor of inosine monophosphate dehydrogenase, adenine is converted to adenosine or inosine monophosphate, either of which, in turn, is converted into inosine, which pairs with adenine, cytosine, and uracil. Purine nucleoside phosphorylase intraconverts inosine and hypoxanthine, Inosine is also an intermediate in a chain of purine nucleotides reactions required for muscle movements. It was tried in the 1970s in Eastern countries for improving athletic performance, nevertheless, the clinical trials for this purpose showed no improvement. It has been shown that inosine has neuroprotective properties and it has been proposed for spinal cord injury, because it improves axonal rewiring, and for administration after stroke, because observation has shown that axonal rewiring is encouraged. After ingestion, inosine produces uric acid that is suggested to be a natural antioxidant, peroxynitrite has been correlated with axon degeneration. In 2003, a study was initiated at the University of Pennsylvania MS Center to determine whether raising the levels of acid by the administration of inosine would slow the progression of MS. The study was completed in 2006 but the results were not reported to NIH, a subsequent publication hinted at potential benefits but the sample size was too small for a definitive conclusion. In addition, the effect of the treatment was the development of kidney stones in four of 16 patients. Thus, additional studies are necessary to prove the treatments efficacy and its phase II trials for Parkinsons disease is now ended, it will continue to phase III trials. Earlier trials had suggested those with the highest serum urate levels had lower progression of Parkinsons symptoms, the trial uses inosine to raise urate levels in those with levels lower than the population mean. Alseres Pharmaceuticals patented the treatment for stroke and is investigating the drug in the MS setting. In the Anatomical Therapeutic Chemical Classification System, it is classified as an antiviral, when designing primers for polymerase chain reaction, inosine is useful in that it can pair with any natural base. This allows for design of primers that span a single-nucleotide polymorphism, however, inosine pairs preferentially with cytidine and its introduction to RNA, e. g. by the action of ADARs, thereby destabilizes double-stranded RNA by changing AU base-pairs to IU mismatches. Despite lack of evidence that it improves muscle development, inosine remains an ingredient in some fitness supplements. Inosine has also found to be an important feed stimulant by itself or in combination with certain amino acids in some species of farmed fish
26.
Mutagen
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In genetics, a mutagen is a physical or chemical agent that changes the genetic material, usually DNA, of an organism and thus increases the frequency of mutations above the natural background level. As many mutations can cause cancer, mutagens are also likely to be carcinogens. Some chemicals only become mutagenic through cellular processes, not all mutations are caused by mutagens, so-called spontaneous mutations occur due to spontaneous hydrolysis, errors in DNA replication, repair and recombination. The first mutagens to be identified were carcinogens, substances that were shown to be linked to cancer. Tumors were described more than 2,000 years before the discovery of chromosomes and DNA, in 500 B. C. the Greek physician Hippocrates named tumors resembling a crab karkinos, meaning crab. In 1775, Sir Percivall Pott wrote a paper on the incidence of scrotal cancer in chimney sweeps. In 1915, Yamagawa and Ichikawa showed that repeated application of coal tar to rabbits ears produced malignant cancer, subsequently, in the 1930s the carcinogen component in coal tar was identified as a polyaromatic hydrocarbon, benzopyrene. Polyaromatic hydrocarbons are also present in soot, which was suggested to be an agent of cancer over 150 years earlier. His collaborator Edgar Altenburg also demonstrated the effect of UV radiation in 1928. Muller went on to use x-rays to create Drosophila mutants that he used in his studies of genetics and he also found that X-rays not only mutate genes in fruit flies but also have effects on the genetic makeup of humans. Similar work by Lewis Stadler also showed the effect of X-ray on barley in 1928. The effect of sunlight had previously noted in the nineteenth century where rural outdoor workers and sailors were found to be more prone to skin cancer. Chemical mutagens were not demonstrated to cause mutation until the 1940s, early studies by Ames showed around 90% of known carcinogens can be identified in Ames test as mutagenic, and ~80% of the mutagens identified through Ames test may also be carcinogens. Mutagens are not necessarily carcinogens, and vice versa, sodium azide for example may be mutagenic, but it has not been shown to be carcinogenic. Mutagens can cause changes to the DNA and are therefore genotoxic and they can affect the transcription and replication of the DNA, which in severe cases can lead to cell death. The mutagen produces mutations in the DNA, and deleterious mutation can result in aberrant, impaired or loss of function for a particular gene, mutagens may therefore be also carcinogens. Different mutagens act on the DNA differently, powerful mutagens may result in chromosomal instability, causing chromosomal breakages and rearrangement of the chromosomes such as translocation, deletion, and inversion. Some mutagens can cause aneuploidy and change the number of chromosomes in the cell, in Ames test, where the varying concentrations of the chemical are used in the test, the dose response curve obtained is nearly always linear, suggesting that there is no threshold for mutagenesis
27.
Deamination
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Deamination is the removal of an amino group from a molecule. Enzymes that catalyse this reaction are called deaminases, in the human body, deamination takes place primarily in the liver, however glutamate is also deaminated in the kidneys. In situations of excess protein intake, deamination is used to break down amino acids for energy, the amino group is removed from the amino acid and converted to ammonia. The rest of the acid is made up of mostly carbon and hydrogen. Ammonia is toxic to the system, and enzymes convert it to urea or uric acid by addition of carbon dioxide molecules in the urea cycle. Urea and uric acid can safely diffuse into the blood and then be excreted in urine, spontaneous deamination is the hydrolysis reaction of cytosine into uracil, releasing ammonia in the process. This can occur in vitro through the use of bisulfite, which deaminates cytosine and this property has allowed researchers to sequence methylated DNA to distinguish non-methylated cytosine and methylated cytosine. In DNA, this spontaneous deamination is corrected for by the removal of uracil by uracil-DNA glycosylase, the resulting abasic site is then recognised by enzymes that break a phosphodiester bond in the DNA, permitting the repair of the resulting lesion by replacement with another cytosine. A DNA polymerase may perform this replacement via nick translation, a terminal excision reaction by its 5-->3 exonuclease activity, DNA ligase then forms a phosphodiester bond to seal the resulting nicked duplex product, which now includes a new, correct cytosine. Spontaneous deamination of 5-methylcytosine results in thymine and ammonia and this is the most common single nucleotide mutation. In DNA, this reaction, if detected prior to passage of the fork, can be corrected by the enzyme thymine-DNA glycosylase. This leaves an abasic site that is repaired by AP endonucleases and polymerase, deamination of guanine results in the formation of xanthine. Xanthine, in an analogous to the enol tautomer of guanine. This results in a transition mutation, where the original G-C base pair transforms into an A-T base pair. Correction of this involves the use of alkyladenine glycosylase during base excision repair. Deamination of adenine results in the formation of hypoxanthine, hypoxanthine, in a manner analogous to the imine tautomer of adenine, selectively base pairs with cytosine instead of thymine. This results in a transition mutation, where the original A-T base pair transforms into a G-C base pair
28.
5-Hydroxymethylcytosine
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5-Hydroxymethylcytosine is a DNA pyrimidine nitrogen base derived from cytosine. It is potentially important in epigenetics, because the group on the cytosine can possibly switch a gene on. It was first seen in bacteriophages in 1952, however, in 2009 it was found to be abundant in human and mouse brains, as well as in embryonic stem cells. In mammals, it can be generated by oxidation of 5-methylcytosine, every mammalian cell seems to contain 5-Hydroxymethylcytosine, but the levels vary significantly depending on the cell type. The highest levels are found in cells of the central nervous system. The amount of hydroxymethylcytosine increases with age, as shown in mouse hippocampus, the exact function of this nitrogen base is still not fully elucidated, but it is thought that it may regulate gene expression or prompt DNA demethylation. This hypothesis is supported by the fact that artificial DNA that contains 5-hydroxymethylcytosines can be converted into unmodified cytosines once introduced into mammalian cells, moreover, 5hmC is highly enriched in primordial germ cells, where it apparently plays a role in global DNA demethylation. 5-Hydroxymethylcytosine may be important in the central nervous system, as it is found in very high levels there. Reduction in the 5-Hydroxymethylcytosine levels have been associated with impaired self-renewal in embryonic stem cells. 5-Hydroxymethylcytosine is also associated with labile, unstable nucleosomes which are frequently repositioned during cell differentiation, 5-Hydroxymethylcytosine was observed by Skirmantas Kriaucionis, an associate at the Heintz lab, who was looking for levels of 5-methylcytosine in two different neuron types. He discovered a significant amount of an unknown substance instead, and after conducting several tests, the lab of L. Aravind used bioinformatic tools to predict that the Tet family of enzymes would likely oxidize 5-methylcytosine to 5-hydroxymethylcytosine. This was demonstrated in vitro and in human and mouse cells by scientists working in the labs of Anjana Rao. 5-Hydroxymethylcytosine was originally observed in mammals in 1972 by R. Yura, Yura found 5-hmC present at extremely high levels in rat brain and liver, completely supplanting 5-methylcytosine. This contradicts all research conducted on mammalian DNA composition conducted before and since, including the Heintz and Rao papers, with the discovery of 5-hydroxymethylcytosine some concerns have been raised regarding DNA methylation studies using the bisulfite sequencing technique. 5-hydroxymethylcytosine has been shown to behave like its precursor, 5-methylcytosine, therefore, bisulfite sequencing data may need to be revisited to verify whether the detected modified base is 5-methylcytosine or 5-hydroxymethylcytosine
29.
Nucleic acid analogue
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Nucleic acid analogues are compounds which are analogous to naturally occurring RNA and DNA, used in medicine and in molecular biology research. Nucleic acids are chains of nucleotides, which are composed of three parts, a backbone, a pentose sugar, either ribose or deoxyribose. An analogue may have any of these altered, typically the analogue nucleobases confer, among other things, different base pairing and base stacking properties. Examples include universal bases, which can pair with all four bases, and phosphate-sugar backbone analogues such as PNA. Nucleic acid analogues are also called Xeno Nucleic Acid and represent one of the pillars of xenobiology. Artificial nucleic acids include peptide nucleic acid, Morpholino and locked nucleic acid, as well as glycol nucleic acid, each of these is distinguished from naturally occurring DNA or RNA by changes to the backbone of the molecule. The artificial nucleotides featured 2 fused aromatic rings, several nucleoside analogues are used as antiviral or anticancer agents. The viral polymerase incorporates these compounds with non-canonical bases and these compounds are activated in the cells by being converted into nucleotides, they are administered as nucleosides since charged nucleotides cannot easily cross cell membranes. To overcome the fact that riboses 2 hydroxy group that reacts with the phosphate linked 3 hydroxy group, the most common RNA analogues are 2-O-methyl-substituted RNA, locked nucleic acid or bridged nucleic acid, morpholino, and peptide nucleic acid. They cannot be synthesized enzymatically and can only be obtained synthetically using phosphoramidite strategy or, for PNA and these nucleoside triphosphates possess a non-canonical sugar, dideoxyribose, which lacks the 3 hydroxyl group normally present in DNA and therefore cannot bond with the next base. The lack of the 3 hydroxyl group terminates the chain reaction as the DNA polymerases mistake it for a regular deoxyribonucleotide, another chain-terminating analogue that lacks a 3 hydroxyl and mimics adenosine is called cordycepin. Cordycepin is a drug that targets RNA replication. Another analogue in sequencing is an analogue, 7-deaza-GTP and is used to sequence CG rich regions, instead 7-deaza-ATP is called tubercidin. Naturally occurring bases can be divided into two classes according to their structure, pyrimidines are six-membered heterocyclic with nitrogen atoms in position 1 and 3, purines are bicyclic, consisting of a pyrimidine fused to an imidazole ring. Artificial nucleotides have been inserted into bacterial DNA but these genes did not template mRNA or induce protein synthesis, the artificial nucleotides featured two fused aromatic rings which formed a complex mimicking the natural base pair. Commonly fluorophores are linked to the ring linked to the sugar via a flexible arm, thiol reactive, thiol containing nucleotides reacts with the fluorophore linked to a reactive leaving group, such as a maleimide. Biotin linked nucleotides rely on the same indirect labelling principle and are used in Affymetrix DNAchips, fluorophores find a variety of uses in medicine and biochemistry. 1, 3-Diaza-2-oxophenothiazine, tC, has a quantum yield of approximately 0.2 both in single- and in double-strands irrespective of surrounding bases
30.
Aminoallyl nucleotide
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Aminoallyl nucleotide is a nucleotide with a modified base containing an allylamine. They are used in post-labeling of nucleic acids by fluorescence detection in microarray and they are reactive with N-Hydroxysuccinimide ester group which helps attach a fluorescent dye to the primary amino group on the nucleotide. These nucleotides are known as 5--nucleotides since the group is usually attached to carbon 5 of the pyrimidine ring of uracil or cytosine. The primary amine group in the aminoallyl moiety is aliphatic and thus more reactive compared to the groups that are directly attached to the rings of the bases. Common names of aminoallyl nucleosides are initially abbreviated with aa- or AA- to indicate aminoallyl, the 5-carbon sugar is indicated with or without the lowercase d indicating deoxyribose if included or ribose if not. Finally the nitrogenous base and number of phosphates are indicated, the goal of combining fluorescence and nucleic acids has been to provide a non-isotopic tag that is detectable to study DNA or RNA. This type of labeling allows scientists to study DNA or RNA in their structure, function, the first base modification for fluorescent labeling occurred in 1971 with a 4-thiouridine and 4-thiouracil. As instrumentation and technologies become more advanced in the field of DNA microarray, better reagents, fluorescent labeling with Cy3 was shown to be more insufficient and skew results, the method of aminoallyl nucleotide incorporation was opted instead. Using aminoallyl nucleotides as indirect fluorescent labeling seemed to nullify the sensitivity issues seen in cyanine-labeling, aminoallyl nucleosides can be synthesized via Heck coupling as shown in the image below. In the image above, on the left is a modified nucleoside with an iodine in the carbon in the pyrimidine ring. The product on the right is used to in molecular biology in RNA synthesis. Other reactions include using a single pot synthesis with other halogens and these nucleotides are used for labeling DNA. Aminoallyl NTPs are used for indirect DNA labeling in PCR, nick translation, primer extensions and these labeled NTPs are helpful because of their application in molecular biology labs where they do not have the capacity to handle radioactive material. For example, 5--Uridine are more effective for high density labeling of DNA than pre-labeling the DNA, after the enzymatic addition of the NTPs, amine reactant fluorescent dyes can be added for detection of the DNA molecule. When incorporated into DNA or RNA molecules by DNA/RNA polymerase, 5--UTP provide a group for the addition of other chemical groups. Thus aminoallyl modified DNA or RNA can be labeled with any compound which has an amine-reactive group, aa-NTPs incorporated into DNA/RNA in combination with a secondary dye coupling reagents can probe for an array analysis. CDNA relies on aminoallyl labeling for detection purposes, although direct labeling of dNTP is the quickest and cheapest method of fluorescent labeling, it is disadvantageous as the sequence allows for only one modified nucleotide for use. Another disadvantage of direct labeling is the bulky nucleotides, however this can be overcome by indirect labeling using aminoallyl modified nucleotides, an easy way to check for labeling success is the color, Good labeling will result in visible blue or red color in the final material
. PMID 24805238.
