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{{Short description|Biological molecules constituting nucleic acids}}
{{Distinguish|nucleoside|nucleobase}}
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[[File:DAMP chemical structure.svg|thumb|275px|class=skin-invert-image|This nucleotide contains the five-carbon sugar [[deoxyribose]] (at center), a [[nucleobase]] called [[adenine]] (upper right), and one [[phosphate]] group (left). The deoxyribose sugar joined only to the nitrogenous base forms a <u title="Nucleotide">[[Deoxyribonucleoside]]</u>  called [[deoxyadenosine]], whereas the whole structure along with the phosphate group is a <u title="Deoxyadenosine monophosphate" href="deoxyadenosine monophosphate">nucleotide</u>, a constituent of DNA with the name [[deoxyadenosine monophosphate]].]]

'''Nucleotides''' are [[Organic compound|organic molecules]] composed of a nitrogenous base, a [[pentose]] sugar and a [[phosphate]]. They serve as [[monomer]]ic units of the [[nucleic acid]] [[polymers]] – [[deoxyribonucleic acid]] (DNA) and [[ribonucleic acid]] (RNA),  both of which are essential [[biomolecules]] within all [[Life|life-forms]] on Earth. Nucleotides are obtained in the diet and are also synthesized from common [[Nutrient|nutrients]] by the [[liver]].<ref name="easy-peasy" />

Nucleotides are composed of three subunit molecules: a [[nucleobase]], a [[pentose|five-carbon sugar]] ([[ribose]] or [[deoxyribose]]), and a phosphate group consisting of one to three [[phosphate]]s.  The four nucleobases in DNA are [[guanine]], [[adenine]], [[cytosine]], and [[thymine]]; in RNA, [[uracil]] is used in place of thymine.

Nucleotides also play a central role in [[metabolism]] at a fundamental, cellular level. They provide chemical energy—in the form of the [[nucleoside triphosphate]]s, [[adenosine triphosphate]] (ATP), [[guanosine triphosphate]] (GTP), [[cytidine triphosphate]] (CTP), and [[uridine triphosphate]] (UTP)—throughout the cell for the many cellular functions that demand energy, including: [[amino acid]], [[protein]] and [[cell membrane]] synthesis, moving the cell and cell parts (both internally and intercellularly), cell division, etc..<ref name=Alberts>Alberts B, Johnson A, Lewis J, Raff M, Roberts K & Walter P (2002). ''Molecular Biology of the Cell'' (4th ed.). Garland Science. {{ISBN|0-8153-3218-1}}. pp. 120–121.</ref> In addition, nucleotides participate in [[cell signaling]] ([[cyclic guanosine monophosphate]] or cGMP and [[cyclic adenosine monophosphate]] or cAMP) and are incorporated into important [[Cofactor (biochemistry)|cofactors]] of enzymatic reactions (e.g., [[coenzyme A]], [[flavin adenine dinucleotide|FAD]], [[flavin mononucleotide|FMN]], [[nicotinamide adenine dinucleotide|NAD]], and [[NADP+|NADP<sup>+</sup>]]).

In experimental [[biochemistry]], nucleotides can be [[radiolabeled]] using [[radionuclide]]s to yield radionucleotides.

'''5-nucleotides''' are also used in [[flavour enhancer]]s as [[food additive]] to enhance the [[umami]] taste, often in the form of a yeast extract.<ref name="nucleotides-flavour-2017">{{Cite journal | vauthors = Abd El-Aleem FS, Taher MS, Lotfy SN, El-Massry KF, Fadel HH |date=2017-12-18 |title=Influence of extracted 5-nucleotides on aroma compounds and flavour acceptability of real beef soup |journal=International Journal of Food Properties |volume=20 |issue=sup1 |pages=S1182–S1194 |doi=10.1080/10942912.2017.1286506|s2cid=100497537 |doi-access=free }}</ref>

== Structure ==
[[File:0322 DNA Nucleotides.jpg|thumb|370px|Showing the arrangement of nucleotides within the structure of nucleic acids: At lower left, a monophosphate nucleotide; its nitrogenous base represents one side of a base-pair. At the upper right, four nucleotides form two base-pairs: thymine and adenine (connected by ''double'' hydrogen bonds) and guanine and cytosine (connected by ''triple'' hydrogen bonds). The individual nucleotide monomers are chain-joined at their sugar and phosphate molecules, forming two 'backbones' (a [[double helix]]) of nucleic acid, shown at upper left.]]

A nucleo<u>tide</u> is composed of three distinctive chemical sub-units: a five-carbon sugar molecule, a [[nucleobase]] (the two of which together are called a [[nucleoside|nucleo<u>side</u>]]), and one [[phosphate group]]. With all three joined, a nucleotide is also termed a "nucleo<u>side</u> ''mono''phosphate", "nucleoside ''di''phosphate" or "nucleoside ''tri''phosphate", depending on how many phosphates make up the phosphate group.<ref>{{Cite book |last=Wiley |url=https://onlinelibrary.wiley.com/doi/book/10.1002/047001590X |title=Encyclopedia of Life Sciences |date=2005-09-09 |publisher=Wiley |isbn=978-0-470-01617-6 |edition=1 |language=en |doi=10.1002/9780470015902.a0001333.pub3}}</ref>

In [[nucleic acid]]s, nucleotides contain either a [[purine]] or a [[pyrimidine]] base—i.e., the nucleobase molecule, also known as a nitrogenous base—and are termed ''ribo''nucleotides if the sugar is ribose, or ''deoxyribo''nucleotides if the sugar is deoxyribose. Individual phosphate molecules repetitively connect the [[ribose|sugar-ring]] molecules in two adjacent nucleotide monomers, thereby connecting the nucleotide monomers of a nucleic acid end-to-end into a long chain. 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 ([[directionality (molecular biology)|directionality]]) of the chain-joins runs from the [[Directionality (molecular biology)#5′-end|5'-end]] to the [[Directionality (molecular biology)#3'-end|3'-end]] (''read'': 5 prime-end to 3 prime-end)—referring to the five carbon sites on sugar molecules in adjacent nucleotides. In a double helix, the two strands are oriented in opposite directions, which permits [[base pairing]] and [[complementarity (molecular biology)|complementarity]] between the base-pairs, all which is essential for [[DNA replication|replicating]] or [[transcription (genetics)|transcribing]] the encoded information found in DNA.{{cn|date=February 2024}}

Nucleic acids, then, are [[polymeric]] [[macromolecule]]s assembled from nucleotides, the [[monomer|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]] (in DNA) and [[uracil]] (in RNA) occur in just one. Adenine forms a [[base pair]] with thymine with two hydrogen bonds, while guanine pairs with cytosine with three hydrogen bonds.

In addition to being building blocks for the construction of nucleic acid polymers, singular nucleotides play roles in cellular energy storage and provision, cellular signaling, as a source of phosphate groups used to modulate the activity of proteins and other signaling molecules, and as enzymatic [[Cofactor (biochemistry)|cofactors]], often carrying out [[redox]] reactions.  Signaling [[cyclic nucleotides]] are formed by binding the phosphate group twice to the same sugar [[Molecular geometry|molecule]], bridging the 5'- and 3'- [[hydroxyl group]]s of the sugar.<ref name="Alberts" />  Some signaling nucleotides differ from the standard single-phosphate group configuration, in having multiple phosphate groups attached to different positions on the sugar.<ref>{{cite book| veditors = Smith AD |title=Oxford Dictionary of Biochemistry and Molecular Biology | edition = Revised |year=2000|location=Oxford|publisher=Oxford University Press|page=460}}</ref>  Nucleotide cofactors include a wider range of chemical groups attached to the sugar via the [[glycosidic bond]], including [[nicotinamide]] and [[Flavin group|flavin]], and in the latter case, the ribose sugar is linear rather than forming the ring seen in other nucleotides.

[[File:Nucleotides 1.svg|class=skin-invert-image|thumb|center|660px|Structural elements of three nucleo<u>tides</u>—where one-, two- or three-phosphates are attached to the nucleo<u>side</u> (in yellow, blue, green) at center: 1st, the nucleotide termed as a ''nucleoside <u>mono</u>phosphate'' is formed by adding a phosphate (in red); 2nd, adding a second phosphate forms a ''nucleoside <u>di</u>phosphate''; 3rd, adding a third phosphate results in a ''nucleoside <u>tri</u>phosphate''. +&nbsp;The nitrogenous base ([[nucleobase]]) is indicated by [[nucleobase|"Base"]] and "[[glycosidic bond]]" (sugar bond). All five [[nucleobase|primary, or canonical, bases]]—the [[purines#Notable purines|purines]] and [[pyrimidine#Nucleotides|pyrimidines]]—are sketched at right (in blue).]]
<div class="skin-invert-image">
{{Gallery
|title=Examples of non-nucleic acid nucleotides
|align=center
|File:Cyclic-AMPchemdraw.png|[[Cyclic adenosine monophosphate|cAMP]], a cyclic nucleotide signaling molecule with a single phosphate linked to both 5- and 3-positions.
|File:PppGpp.svg|[[Guanosine pentaphosphate|pppGpp]], a nucleotide signaling molecule with both 5'- and 3'-phosphates.
|File:NADP+ phys.svg|[[Nicotinamide adenine dinucleotide phosphate|NADP]], a dinucleotide enzymatic [[Cofactor (biochemistry)|cofactor]].
|File:FAD.png|[[Flavin adenine dinucleotide|FAD]], a dinucleotide enzymatic cofactor in which one of the ribose sugars adopts a linear configuration rather than a ring.}}
</div>

==Synthesis==
Nucleotides can be [[Nucleic acid metabolism|synthesized]] by a variety of means, both [[in vitro]] and [[in vivo]].{{cn|date=February 2024}}

In vitro, [[protecting group]]s may be used during laboratory production of nucleotides. A purified [[nucleoside]] is protected to create a [[phosphoramidite]], which can then be used to obtain analogues not found in nature and/or to [[oligonucleotide synthesis|synthesize an oligonucleotide]].{{cn|date=February 2024}}

In vivo, nucleotides can be synthesized [[de novo synthesis|de novo]] or recycled through [[nucleotide salvage|salvage pathways]].<ref name = "easy-peasy" >{{cite journal | vauthors = Zaharevitz DW, Anderson LW, Malinowski NM, Hyman R, Strong JM, Cysyk RL | title = Contribution of de-novo and salvage synthesis to the uracil nucleotide pool in mouse tissues and tumors in vivo | journal = European Journal of Biochemistry | volume = 210 | issue = 1 | pages = 293–6 | date = November 1992 | pmid = 1446677 | doi=10.1111/j.1432-1033.1992.tb17420.x| doi-access = free }}</ref> 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. Recently it has been also demonstrated that cellular bicarbonate metabolism can be regulated by [[mTORC1]] signaling.<ref>{{cite journal | vauthors = Ali E, Liponska A, O'Hara B, Amici D, Torno M, Gao P, Asara J, Yap M-N F, Mendillo M, Ben-Sahra I | title = The mTORC1-SLC4A7 axis stimulates bicarbonate import to enhance de novo nucleotide synthesis | journal = Molecular Cell | volume = 82 | issue = 1 | pages = 3284–3298.e7 | date = June 2022 | doi = 10.1016/j.molcel.2022.06.008 | pmid = 35772404 | pmc = 9444906 }}</ref> The liver is the major organ of de novo synthesis of all four nucleotides. De novo synthesis of pyrimidines and purines follows two different pathways. Pyrimidines are synthesized first from aspartate and carbamoyl-phosphate in the cytoplasm to the common precursor ring structure orotic acid, onto which a phosphorylated ribosyl unit is covalently linked. 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, not within a specific [[organelle]]. Nucleotides undergo breakdown such that useful parts can be reused in synthesis reactions to create new nucleotides.{{cn|date=February 2024}}

===Pyrimidine ribonucleotide synthesis===
[[File:Nucleotides syn2.png|thumb|right|400px|The synthesis of [[Uridine monophosphate|UMP]].
{{legend|blue|enzymes}}
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{{legend|rgb(227,13,196)|metal ions}}
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{{main|Pyrimidine metabolism}}
The synthesis of the pyrimidines [[cytidine triphosphate]] (CTP) and [[uridine triphosphate]] (UTP) occurs in the cytoplasm and starts with the formation of [[carbamoyl phosphate]] from [[glutamine]] and CO<sub>2</sub>. Next, [[aspartate carbamoyltransferase]] catalyzes a condensation reaction between [[aspartate]] and carbamoyl phosphate to form [[carbamoyl aspartic acid]], which is cyclized into [[4,5-dihydroorotic acid]] by [[dihydroorotase]]. The latter is converted to [[orotate]] by [[dihydroorotate oxidase]]. The net reaction is:

:(''S'')-Dihydroorotate + O<sub>2</sub> → Orotate + H<sub>2</sub>O<sub>2</sub>

Orotate is covalently linked with a phosphorylated ribosyl unit. The covalent linkage between the ribose and pyrimidine occurs at position C<sub>1</sub><ref>See [[IUPAC nomenclature of organic chemistry]] for details on carbon residue numbering</ref> of the [[ribose]] unit, which contains a [[pyrophosphate]], and N<sub>1</sub> of the pyrimidine ring. [[Orotate phosphoribosyltransferase]] (PRPP transferase) catalyzes the net reaction yielding [[Orotidine 5'-monophosphate]] (OMP):

:Orotate + [[Phosphoribosyl pyrophosphate|5-Phospho-α-D-ribose 1-diphosphate (PRPP)]]  →  Orotidine 5'-phosphate + Pyrophosphate

Orotidine 5'-monophosphate is decarboxylated by [[orotidine-5'-phosphate decarboxylase]] to form [[uridine monophosphate]] (UMP). PRPP transferase catalyzes both the ribosylation and decarboxylation reactions, forming UMP from orotic acid in the presence of PRPP. It is from UMP that other pyrimidine nucleotides are derived.  UMP is phosphorylated by two kinases to uridine triphosphate (UTP) via two sequential reactions with ATP.  First, the diphosphate from UDP is produced, which in turn is phosphorylated to UTP. Both steps are fueled by ATP hydrolysis:

:ATP + UMP → ADP + UDP

:UDP + ATP → UTP + ADP

CTP is subsequently formed by the amination of UTP by the catalytic activity of [[CTP synthetase]]. Glutamine is the NH<sub>3</sub> donor and the reaction is fueled by ATP hydrolysis, too:

:UTP + Glutamine + ATP + H<sub>2</sub>O → CTP + ADP + P<sub>i</sub>

[[Cytidine monophosphate]] (CMP) is derived from cytidine triphosphate (CTP) with subsequent loss of two phosphates.<ref>{{cite journal | vauthors = Jones ME | title = Pyrimidine nucleotide biosynthesis in animals: genes, enzymes, and regulation of UMP biosynthesis | journal = Annual Review of Biochemistry | volume = 49 | issue = 1 | pages = 253–79 | date = 1980 | pmid = 6105839 | doi = 10.1146/annurev.bi.49.070180.001345 }}</ref><ref>{{cite book |title=The organic chemistry of biological pathways |vauthors=McMurry JE, Begley TP |date=2005 |publisher=Roberts & Company |isbn=978-0-9747077-1-6}}
</ref>

===Purine ribonucleotide synthesis===

{{main|Purine metabolism}}

The atoms that are used to build the [[purine nucleotides]] come from a variety of sources:
[[File:Nucleotide synthesis.svg|thumb|250px|class=skin-invert-image|'''The [[biosynthetic]] origins of purine ring [[atoms]]'''<br /><br />N<sub>1</sub> arises from the amine group of [[Aspartic acid|Asp]]<br />C<sub>2</sub> and C<sub>8</sub> originate from [[formate]]<br />N<sub>3</sub> and N<sub>9</sub> are contributed by the amide group of [[Glutamine|Gln]]<br />C<sub>4</sub>, C<sub>5</sub> and N<sub>7</sub> are derived from [[Glycine|Gly]] <br />C<sub>6</sub> comes from HCO<sub>3</sub><sup>−</sup> (CO<sub>2</sub>)]]
[[File:Nucleotides syn1.svg|class=skin-invert-image|thumb|600px|Diagram of the synthesis of IMP.
{{legend|blue|enzymes}}
{{legend|rgb(219,155,36)|coenzymes}}
{{legend|rgb(151,149,45)|substrate names}}
{{legend|rgb(227,13,196)|metal ions}}
{{legend|rgb(128,0,0)|inorganic molecules}}]]

The [[de novo synthesis]] of [[purine nucleotides]] by which these precursors are incorporated into the purine ring proceeds by a 10-step pathway to the branch-point intermediate [[Inosine monophosphate|IMP]], the nucleotide of the base [[hypoxanthine]]. [[Adenosine monophosphate|AMP]] and [[Guanosine monophosphate|GMP]] are subsequently synthesized from this intermediate via separate, two-step pathways. Thus, purine [[Moiety (chemistry)|moieties]] are initially formed as part of the [[ribonucleotides]] rather than as [[Freebase (chemistry)|free bases]].

Six enzymes take part in IMP synthesis. Three of them are multifunctional:
* [[Phosphoribosylglycinamide formyltransferase|GART]] (reactions 2, 3, and 5)
* [[Phosphoribosylaminoimidazole carboxylase|PAICS]] (reactions 6, and 7)
* [[Inosine monophosphate synthase|ATIC]] (reactions 9, and 10)

The pathway starts with the formation of [[PRPP]]. [[PRPS1]] is the [[enzyme]] that activates [[R5P]], which is formed primarily by the [[pentose phosphate pathway]], to PRPP by reacting it with [[Adenosine triphosphate|ATP]]. The reaction is unusual in that a pyrophosphoryl group is directly transferred from ATP to C<sub>1</sub> of R5P and that the product has the '''α''' configuration about C1. This reaction is also shared with the pathways for the synthesis of [[Tryptophan|Trp]], [[Histidine|His]], and the [[pyrimidine nucleotides]]. Being on a major metabolic crossroad and requiring much energy, this reaction is highly regulated.

In the first reaction unique to purine nucleotide biosynthesis, [[PPAT]] catalyzes the displacement of PRPP's [[pyrophosphate]] group (PP<sub>i</sub>) by an amide nitrogen donated from either [[glutamine]] (N), [[glycine]] (N&C), [[aspartate]] (N), [[folic acid]] (C<sub>1</sub>), or CO<sub>2</sub>. This is the committed step in purine synthesis. The reaction occurs with the inversion of configuration about ribose C<sub>1</sub>, thereby forming '''β'''-[[5-phosphorybosylamine]] (5-PRA) and establishing the anomeric form of the future nucleotide.

Next, a glycine is incorporated fueled by ATP hydrolysis, and the carboxyl group forms an amine bond to the NH<sub>2</sub> previously introduced. A one-carbon unit from folic acid coenzyme N<sub>10</sub>-formyl-THF is then added to the amino group of the substituted glycine followed by the closure of the imidazole ring. Next, a second NH<sub>2</sub> group is transferred from glutamine to the first carbon of the glycine unit. A carboxylation of the second carbon of the glycin unit is concomitantly added. This new carbon is modified by the addition of a third NH<sub>2</sub> unit, this time transferred from an aspartate residue. Finally, a second one-carbon unit from formyl-THF is added to the nitrogen group and the ring is covalently closed to form the common purine precursor inosine monophosphate (IMP).

Inosine monophosphate is converted to adenosine monophosphate in two steps. First, GTP hydrolysis fuels the addition of aspartate to IMP by adenylosuccinate synthase, substituting the carbonyl oxygen for a nitrogen and forming the intermediate adenylosuccinate. Fumarate is then cleaved off forming adenosine monophosphate. This step is catalyzed by adenylosuccinate lyase.

Inosine monophosphate is converted to guanosine monophosphate by the oxidation of IMP forming xanthylate, followed by the insertion of an amino group at C<sub>2</sub>.  NAD<sup>+</sup> is the electron acceptor in the oxidation reaction. The amide group transfer from glutamine is fueled by ATP hydrolysis.

===Pyrimidine and purine degradation===
In humans, pyrimidine rings (C, T, U) can be degraded completely to CO<sub>2</sub> and NH<sub>3</sub> (urea excretion). That having been said, purine rings (G, A) cannot. Instead, they are degraded to the metabolically inert [[uric acid]] which is then excreted from the body. Uric acid is formed when GMP is split into the base guanine and ribose. Guanine is deaminated to xanthine which in turn is oxidized to uric acid. This last reaction is irreversible. Similarly, uric acid can be formed when AMP is deaminated to IMP from which the ribose unit is removed to form hypoxanthine. Hypoxanthine is oxidized to xanthine and finally to uric acid. Instead of uric acid secretion, guanine and IMP can be used for recycling purposes and nucleic acid synthesis in the presence of PRPP and aspartate (NH<sub>3</sub> donor).{{cn|date=February 2024}}

==Prebiotic synthesis of nucleotides==
{{One source section
| date = November 2025
}}
Theories about the [[Abiogenesis|origin of life]] require knowledge of chemical pathways that permit formation of life's key building blocks under plausible prebiotic conditions.  The [[RNA world]] hypothesis holds that in the [[primordial soup]] there existed free-floating [[ribonucleotide]]s, the fundamental molecules that combine in series to form [[RNA]].  Complex molecules like RNA must have arisen from small molecules whose reactivity was governed by physico-chemical processes.  RNA is composed of [[purine]] and [[pyrimidine]] nucleotides, both of which are necessary for reliable information transfer, and thus Darwinian [[evolution]].  Becker et al. showed how pyrimidine [[nucleoside]]s can be synthesized from small molecules and [[ribose]], driven solely by wet-dry cycles.<ref name="Becker2019">{{cite journal | vauthors = Becker S, Feldmann J, Wiedemann S, Okamura H, Schneider C, Iwan K, Crisp A, Rossa M, Amatov T, Carell T | title = Unified prebiotically plausible synthesis of pyrimidine and purine RNA ribonucleotides | journal = Science | volume = 366 | issue = 6461 | pages = 76–82 | date = October 2019 | pmid = 31604305 | doi = 10.1126/science.aax2747 | s2cid = 203719976 | bibcode = 2019Sci...366...76B | url = http://nbn-resolving.de/urn:nbn:de:bvb:19-epub-71503-3 }}</ref>  Purine nucleosides can be synthesized by a similar pathway.  5'-mono- and di-phosphates also form selectively from phosphate-containing minerals, allowing concurrent formation of [[polynucleotide|polyribonucleotides]] with both the purine and pyrimidine bases.  Thus a reaction network towards the purine and pyrimidine RNA building blocks can be established starting from simple atmospheric or volcanic molecules.<ref name = Becker2019/>

==Unnatural base pair (UBP)==

{{Main|Base pair#Unnatural base pair (UBP)}}

An unnatural base pair (UBP) is a designed subunit (or [[nucleobase]]) of [[DNA]] which is created in a laboratory and does not occur in nature.<ref name="Malyshev PNAS 20120724">{{cite journal | vauthors = Malyshev DA, Dhami K, Quach HT, Lavergne T, Ordoukhanian P, Torkamani A, Romesberg FE | title = Efficient and sequence-independent replication of DNA containing a third base pair establishes a functional six-letter genetic alphabet | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 30 | pages = 12005–10 | date = July 2012 | pmid = 22773812 | pmc = 3409741 | doi = 10.1073/pnas.1205176109 | bibcode = 2012PNAS..10912005M | doi-access = free }}</ref> Examples include [[d5SICS]] and [[dNaM]]. These artificial nucleotides bearing hydrophobic [[nucleobase]]s, feature two fused [[Aromatic hydrocarbon|aromatic rings]] that form a (d5SICS–dNaM) complex or base pair in DNA.<ref name="NATJ-20140507" /><ref name="Ewan">{{cite news| url=http://www.huffingtonpost.com/2014/05/07/living-organism-artificial-dna_n_5283095.html |title=Scientists Create First Living Organism With 'Artificial' DNA| vauthors = Callaway E |date=May 7, 2014| work=Nature News| publisher=Huffington Post| access-date=8 May 2014}}</ref> ''E. coli'' have been induced to replicate a plasmid containing UBPs through multiple generations.<ref name="Fikes">{{cite news| url=http://www.utsandiego.com/news/2014/may/08/tp-life-engineered-with-expanded-genetic-code/| title=Life engineered with expanded genetic code| vauthors = Fikes BJ | date=May 8, 2014 |work=San Diego Union Tribune| access-date=8 May 2014}}</ref> This is the first known example of a living organism passing along an expanded genetic code to subsequent generations.<ref name="NATJ-20140507">{{cite journal | vauthors = Malyshev DA, Dhami K, Lavergne T, Chen T, Dai N, Foster JM, Corrêa IR, Romesberg FE | title = A semi-synthetic organism with an expanded genetic alphabet | journal = Nature | volume = 509 | issue = 7500 | pages = 385–8 | date = May 2014 | pmid = 24805238 | pmc = 4058825 | doi = 10.1038/nature13314 | bibcode = 2014Natur.509..385M }}</ref><ref name="Sample">{{cite news| url=https://www.theguardian.com/world/2014/may/07/living-organism-pass-down-artificial-dna-us-scientists| title=First life forms to pass on artificial DNA engineered by US scientists| vauthors = Sample I |date=May 7, 2014|work=The Guardian|access-date=8 May 2014}}</ref>

==Medical applications of synthetic nucleotides==
The applications of synthetic nucleotides vary widely and include disease diagnosis, treatment, or precision medicine. 

# '''Antiviral or Antiretroviral agents:''' several nucleotide derivatives have been used in the treatment against infection with [[Hepatitis]] and [[HIV]].<ref>{{cite journal | vauthors = Ramesh D, Vijayakumar BG, Kannan T | title = Therapeutic potential of uracil and its derivatives in countering pathogenic and physiological disorders | journal = European Journal of Medicinal Chemistry | volume = 207 | article-number = 112801 | date = December 2020 | pmid = 32927231 | doi = 10.1016/j.ejmech.2020.112801 | s2cid = 221724578 }}</ref><ref>{{cite journal | vauthors = Ramesh D, Vijayakumar BG, Kannan T | title = Advances in Nucleoside and Nucleotide Analogues in Tackling Human Immunodeficiency Virus and Hepatitis Virus Infections | journal = ChemMedChem | volume = 16 | issue = 9 | pages = 1403–1419 | date = May 2021 | pmid = 33427377 | doi = 10.1002/cmdc.202000849 | url = https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.202000849 | access-date = 13 March 2021 | url-status = dead | s2cid = 231576801 | archive-url = https://web.archive.org/web/20211214220544/https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.202000849 | archive-date = 14 December 2021 | url-access = subscription }}</ref> Examples of direct nucleoside analog reverse-transcriptase inhibitors ([[Reverse-transcriptase inhibitor|NRTIs]]) include [[Tenofovir disoproxil]], [[Tenofovir alafenamide]], and [[Sofosbuvir]]. On the other hand, agents such as [[Mericitabine]], [[Lamivudine]], [[Entecavir]] and [[Telbivudine]] must first undergo metabolization via phosphorylation to become activated. 
# '''Antisense oligonucleotides (ASO)''': synthetic [[Oligonucleotide|oligonucleotides]] have been used in the treatment of rare heritable diseases since they can bind specific [[RNA]] transcripts and ultimately modulate protein expression. [[Spinal muscular atrophy]], [[ALS|amyotrophic lateral sclerosis]], [[Familial hypercholesterolemia|homozygous familial hypercholesterolemia]], and [[Primary hyperoxaluria|primary hyperoxaluria type 1]] are all amenable to ASO-based therapy.<ref>{{cite journal | vauthors = Lauffer MC, van Roon-Mom W, Aartsma-Rus A | title = Possibilities and limitations of antisense oligonucleotide therapies for the treatment of monogenic disorders | journal = Communications Medicine | volume = 4 | issue = 1 | article-number = 6 | date = January 2024 | pmid = 38182878 | pmc = 10770028 | doi = 10.1038/s43856-023-00419-1 }}</ref> The application of oligonucleotides is a new frontier in precision medicine and management of conditions which are untreatable.
# '''Synthetic guide RNA (gRNA)''': synthetic nucleotides can be used to design [[Guide RNA|gRNA]] which are essential for the proper function of gene-editing technologies such as [[CRISPR gene editing|CRISPR-Cas9]]. 

== Length unit ==
Nucleotide (abbreviated "nt") is a common unit of length for single-stranded nucleic acids, similar to how [[base pair]] is a unit of length for double-stranded nucleic acids.<ref>{{Cite web |title=Biology Terms Dictionary: nt |url=https://www.genscript.com/biology-glossary/2079/nt |access-date=July 31, 2023 |website=GenScript}}</ref>

== Abbreviation codes for degenerate bases ==
{{main|Nucleic acid notation}}

The [[IUPAC]] has designated the symbols for nucleotides.<ref name="iupac">{{cite web |url=http://www.chem.qmul.ac.uk/iubmb/misc/naseq.html |author=Nomenclature Committee of the International Union of Biochemistry (NC-IUB) |title=Nomenclature for Incompletely Specified Bases in Nucleic Acid Sequences |date=1984 |access-date=2008-02-04}}</ref> Apart from the five (A, G, C, T/U) bases, often degenerate bases are used especially for designing [[Primer (molecular biology)|PCR primers]]. These nucleotide codes are listed here.  Some primer sequences may also include the character "I", which codes for the non-standard nucleotide [[inosine]].  Inosine occurs in [[tRNAs]] and will pair with adenine, cytosine, or thymine.  This character does not appear in the following table, however, because it does not represent a degeneracy.  While inosine can serve a similar function as the degeneracy "H", it is an actual nucleotide, rather than a representation of a mix of nucleotides that covers each possible pairing needed.

{| class="wikitable" style="vertical-align:top; margin-left:25px; margin-top:10px; margin-right:25px; margin-bottom:25px; text-align:center;"
|-
! Symbol<ref name="iupac"/> !! Description !!colspan=5| Bases represented
|-
| '''A''' || align="left" | '''a'''denine || A || || || ||rowspan=5| 1
|-
| '''C''' || align="left" | '''c'''ytosine || || C || ||
|-
| '''G''' || align="left" | '''g'''uanine || || || G ||
|-
| '''T''' || align="left" | '''t'''hymine || || || || T
|-
| '''U''' || align="left" | '''u'''racil || || || || U
|- bgcolor=#e8e8e8
| '''W''' ||align=left| '''w'''eak || A || || || T ||rowspan=6| 2
|- bgcolor=#e8e8e8
| '''S''' ||align=left| '''s'''trong || || C || G ||
|- bgcolor=#e8e8e8
| '''M''' ||align=left| [[Amine|a'''m'''ino]] || A || C || ||
|- bgcolor=#e8e8e8
| '''K''' ||align=left| [[Ketone|'''k'''eto]] || || || G || T
|- bgcolor=#e8e8e8
| '''R''' ||align=left| [[Purine|pu'''r'''ine]] || A || || G ||
|- bgcolor=#e8e8e8
| '''Y''' ||align=left| [[Pyrimidine|p'''y'''rimidine]] || || C || || T
|-
| '''B''' ||align=left|  not A ('''B''' comes after A) || || C || G || T  ||rowspan=4| 3
|-
| '''D''' ||align=left|  not C ('''D''' comes after C) || A || || G || T
|-
| '''H''' ||align=left| not G ('''H''' comes after G)|| A || C || || T
|-
| '''V''' ||align=left| not T ('''V''' comes after T and U) || A || C || G ||
|- bgcolor=#e8e8e8
| '''N''' ||align=left|  a'''n'''y base (not a gap) || A || C || G || T || 4
|}

== See also ==
{{Portal|Biology}}
{{colbegin}}
* [[Biology]]
* [[Chromosome]]
* [[Gene]]
* [[Genetics]]
* {{annotated link|Nucleic acid analogue}}
* {{annotated link|Nucleic acid sequence}}
* {{annotated link|Nucleobase}}
{{colend}}

== References ==
{{reflist|30em}}

== Further reading ==
{{refbegin}}
* {{cite book | vauthors = Sigel A, Operschall BP, Sigel H | chapter = Chapter 11. Complex Formation of Lead(II) with Nucleotides and Their Constituents | pages = 319–402 | publisher = de Gruyter | date = 2017 | series = Metal Ions in Life Sciences | volume = 17 | title = Lead: Its Effects on Environment and Health | veditors = Astrid S, Helmut S, Sigel RK | doi = 10.1515/9783110434330-011 | pmid = 28731304 | isbn = 9783110434330 }}
* {{cite journal | vauthors = Freisinger E, Sigel RK | title = From nucleotides to ribozymes—a comparison of their metal ion binding properties. | journal = Coordination Chemistry Reviews | date = July 2007 | volume = 251 | issue = 13–14 | pages = 1834–1851 | doi = 10.1016/j.ccr.2007.03.008 | url = https://www.zora.uzh.ch/id/eprint/59908/1/ZORA_.59908_FromNucleotidesToRibozymes.pdf }}
* {{cite journal | author = IUPAC-IUB Commission on Biochemical Nomenclature (CBN) |title=Abbreviations and Symbols for Nucleic Acids, Polynucleotides and their Constituents |journal=Journal of Molecular Biology |date=14 February 1971 |volume=55 |issue=3 |pages=299–310 |doi=10.1016/0022-2836(71)90319-6|pmid=5551389 }}
* {{cite book |chapter=Chapter P-10 Parent Structures for Natural Products and Related Compounds |chapter-url=https://iupac.qmul.ac.uk/BlueBook/PDF/P10.pdf |veditors=Favre HA, Powell WH |title=Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013 |date=2014 |publisher=Royal Soc. of Chemistry |location=Cambridge |isbn=978-0-85404-182-4 }}
* {{cite web | date = 2003 | work = Clackamas Community College | veditors = Bender H | title = Nucleotide Structure | url = http://dl.clackamas.cc.or.us/ch106-09/nucleoti.htm | access-date = 2020-04-21 | archive-date = 2006-09-01 | archive-url = https://web.archive.org/web/20060901043124/http://dl.clackamas.cc.or.us/ch106-09/nucleoti.htm | url-status = dead }}
{{refend}}

{{Genetics|state=uncollapsed}}
{{Nucleotide metabolism intermediates}}
{{Nucleobases, nucleosides, and nucleotides}}
{{Purinergics}}
{{Authority control}}

[[Category:Nucleotides| ]]
[[Category:DNA]]
[[Category:Molecular biology]]