Thymidine (

symbol A symbol is a mark, sign, or word that indicates, signifies, or is understood as representing an idea, object, or relationship. Symbols allow people to go beyond what is known or seen by creating linkages between otherwise very different conc ...

dT or dThd), also known as deoxythymidine, deoxyribosylthymine, or thymine deoxyriboside, is a

pyrimidine Pyrimidine (; ) is an aromatic, heterocyclic, organic compound similar to pyridine (). One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. The other ...

deoxynucleoside A deoxyribonucleotide is a nucleotide that contains deoxyribose. They are the monomeric units of the informational biopolymer, deoxyribonucleic acid ( DNA). Each deoxyribonucleotide comprises three parts: a deoxyribose sugar ( monosaccharide), a n ...

. Deoxythymidine is the DNA

nucleoside Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar (ribose or 2'-deoxyribose) whereas a nucleotide ...

T, which pairs with

deoxyadenosine Deoxyadenosine (symbol dA or dAdo) is a deoxyribonucleoside. It is a derivative of the nucleoside adenosine, differing from the latter by the replacement of a hydroxyl group (-OH) by hydrogen (-H) at the 2′ position of its ribose sugar moiety. D ...

(A) in double-stranded DNA. In cell biology it is used to synchronize the cells in G1/early S phase. The prefix deoxy- is often left out since there are no precursors of thymine nucleotides involved in RNA synthesis. Before the boom in thymidine use caused by the need for thymidine in the production of the

antiretroviral drug The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs as a strategy to control HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle. The use of multiple ...

azidothymidine Zidovudine (ZDV), also known as azidothymidine (AZT), is an antiretroviral medication used to prevent and treat HIV/AIDS. It is generally recommended for use in combination with other antiretrovirals. It may be used to prevent mother-to-child ...

(AZT), much of the world's thymidine production came from

herring Herring are forage fish, mostly belonging to the family of Clupeidae. Herring often move in large schools around fishing banks and near the coast, found particularly in shallow, temperate waters of the North Pacific and North Atlantic Oceans, i ...

sperm. Thymidine occurs almost exclusively in DNA but it also occurs in the T-loop of

tRNA Transfer RNA (abbreviated tRNA and formerly referred to as sRNA, for soluble RNA) is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes), that serves as the physical link between the mRNA and the amino ac ...

Structure and properties

In its composition, deoxythymidine is a

composed of

deoxyribose Deoxyribose, or more precisely 2-deoxyribose, is a monosaccharide with idealized formula H−(C=O)−(CH2)−(CHOH)3−H. Its name indicates that it is a deoxy sugar, meaning that it is derived from the sugar ribose by loss of a hydroxy group. D ...

(a pentose

sugar Sugar is the generic name for sweet-tasting, soluble carbohydrates, many of which are used in food. Simple sugars, also called monosaccharides, include glucose, fructose, and galactose. Compound sugars, also called disaccharides or double ...

) joined to the

base

thymine Thymine () ( symbol T or Thy) is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine nu ...

. Deoxythymidine can be phosphorylated with one, two or three phosphoric acid groups, creating

dTMP Thymidine monophosphate (TMP), also known as thymidylic acid (conjugate base thymidylate), deoxythymidine monophosphate (dTMP), or deoxythymidylic acid (conjugate base deoxythymidylate), is a nucleotide that is used as a monomer in DNA. It is an ...

(deoxythymidine monophosphate),

dTDP Thymidine diphosphate (TDP) or deoxythymidine diphosphate (dTDP) (also thymidine pyrophosphate, dTPP) is a nucleotide diphosphate. It is an ester of pyrophosphoric acid with the nucleoside thymidine. dTDP consists of the pyrophosphate group, the p ...

, or

dTTP Deoxythymidine triphosphate (dTTP) is one of the four nucleoside triphosphates that are used in the ''in vivo'' synthesis of DNA. Unlike the other deoxyribonucleoside triphosphates, thymidine triphosphate does not always contain the "deoxy" prefi ...

(for the di- and tri- phosphates, respectively). It exists in

solid Solid is one of the State of matter#Four fundamental states, four fundamental states of matter (the others being liquid, gas, and Plasma (physics), plasma). The molecules in a solid are closely packed together and contain the least amount o ...

form as small white

crystals A crystal or crystalline solid is a solid material whose constituents (such as atoms, molecules, or ions) are arranged in a highly ordered microscopic structure, forming a crystal lattice that extends in all directions. In addition, macrosc ...

or white crystalline

powder A powder is a dry, bulk solid composed of many very fine particles that may flow freely when shaken or tilted. Powders are a special sub-class of granular materials, although the terms ''powder'' and ''granular'' are sometimes used to distin ...

. It has a

molecular weight A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...

of 242.229 u and a

melting point The melting point (or, rarely, liquefaction point) of a substance is the temperature at which it changes state from solid to liquid. At the melting point the solid and liquid phase exist in equilibrium. The melting point of a substance depends ...

of 185

°C The degree Celsius is the unit of temperature on the Celsius scale (originally known as the centigrade scale outside Sweden), one of two temperature scales used in the International System of Units (SI), the other being the Kelvin scale. The ...

. The stability of deoxythymidine under

standard temperature and pressure Standard temperature and pressure (STP) are standard sets of conditions for experimental measurements to be established to allow comparisons to be made between different sets of data. The most used standards are those of the International Union o ...

(STP) is very high. Deoxythymidine is non-toxic and as part of one of the four nucleosides in DNA it is a naturally occurring compound that exists in all living organisms and DNA viruses. Instead of thymidine, RNA contains

uridine Uridine (symbol U or Urd) is a glycosylated pyrimidine analog containing uracil attached to a ribose ring (or more specifically, a ribofuranose) via a β-N1-glycosidic bond. The analog is one of the five standard nucleosides which make up nuclei ...

(

uracil Uracil () (symbol U or Ura) is one of the four nucleobases in the nucleic acid RNA. The others are adenine (A), cytosine (C), and guanine (G). In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced by ...

joined to

ribose Ribose is a simple sugar and carbohydrate with molecular formula C5H10O5 and the linear-form composition H−(C=O)−(CHOH)4−H. The naturally-occurring form, , is a component of the ribonucleotides from which RNA is built, and so this compo ...

). Uracil is chemically very similar to thymine, which is also known as 5-methyluracil. Since thymine nucleotides are precursors of DNA (but not RNA), the prefix "deoxy" is often left out, i.e., deoxythymidine is often just called thymidine. Thymidine is listed as a chemical teratogen.

Modified analogs

Iododeoxyuridine Idoxuridine is an anti-herpesvirus antiviral drug. It is a nucleoside analogue, a modified form of deoxyuridine, similar enough to be incorporated into viral DNA replication, but the iodine atom added to the uracil component blocks base pairin ...

is a radiosensitizer and increases the amount of DNA damage received from ionizing radiation.

Azidothymidine Zidovudine (ZDV), also known as azidothymidine (AZT), is an antiretroviral medication used to prevent and treat HIV/AIDS. It is generally recommended for use in combination with other antiretrovirals. It may be used to prevent mother-to-child ...

(AZT) – used in the treatment of

HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...

infection. AZT inhibits the process of reverse transcription, a critical step in the

viral life cycle Viruses are only able to Replicate (biology), replicate themselves by commandeering the reproductive apparatus of cells and making them reproduce the virus's genetic structure and virion, particles instead. How viruses do this depends mainly on t ...

Radiolabeled A radioactive tracer, radiotracer, or radioactive label is a chemical compound in which one or more atoms have been replaced by a radionuclide so by virtue of its radioactive decay it can be used to explore the mechanism of chemical reactions by tr ...

thymidine (TdR), such as tritiated thymidine (³H-TdR), is commonly used in cell proliferation assays. The thymidine is incorporated into dividing cells and the level of this incorporation, measured using a liquid scintillation counter, is proportional to the amount of cell proliferation. For example,

lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...

proliferation can be measured this way in

lymphoproliferative disorders Lymphoproliferative disorders (LPDs) refer to a specific class of diagnoses, comprising a group of several conditions, in which lymphocytes are produced in excessive quantities. These disorders primarily present in patients who have a compromised i ...

Bromodeoxyuridine Bromodeoxyuridine (5-bromo-2'-deoxyuridine, BrdU, BUdR, BrdUrd, broxuridine) is a synthetic nucleoside analogue with a chemical structure similar to thymidine. BrdU is commonly used to study cell proliferation in living tissues and has been stud ...

(BrdU) is another thymidine analog that is often used for the detection of proliferating cells in living tissues. 5-Ethynyl-2´-deoxyuridine (EdU) is a thymidine analog which is incorporated into the DNA of dividing cells and is used to assay DNA synthesis in cell culture or living tissues. It can be visualized by covalently binding a fluorescent azide using

click chemistry In chemical synthesis, click chemistry is a class of biocompatible small molecule reactions commonly used in bioconjugation, allowing the joining of substrates of choice with specific biomolecules. Click chemistry is not a single specific reaction ...

, which is less harsh than the conditions used to expose the

epitope An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The epitope is the specific piece of the antigen to which an antibody binds. The p ...

for BrdU antibodies.

Edoxudine Edoxudine (or edoxudin) is an antiviral drug. It is an analog of thymidine, a nucleoside Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also terme ...

is an

antiviral drug Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do n ...

Telbivudine Telbivudine is an antiviral drug used in the treatment of hepatitis B infection. It is marketed by Swiss pharmaceutical company Novartis under the trade names Sebivo (European Union) and Tyzeka (United States). Clinical trials have shown it to be ...

(β-L-2'-deoxythymidine, LdT) is the unmodified "unnatural" L-

enantiomer In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical ant ...

of thymidine that was used in the treatment of chronic

hepatitis B Hepatitis B is an infectious disease caused by the ''Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. Fo ...

Thymidine imbalance induces mutation and recombination

During growth of

bacteriophage T4 Escherichia virus T4 is a species of bacteriophages that infect ''Escherichia coli'' bacteria. It is a double-stranded DNA virus in the subfamily '' Tevenvirinae'' from the family Myoviridae. T4 is capable of undergoing only a lytic lifecycle ...

, an excess of thymidine availability increases

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...

.Bernstein C, Bernstein H, Mufti S, Strom B. Stimulation of mutation in phage T 4 by lesions in gene 32 and by thymidine imbalance. Mutat Res. 1972 Oct;16(2):113-9. doi: 10.1016/0027-5107(72)90171-6. PMID: 4561494 A deficiency of thymidine during growth also increases mutation. A thymidylate auxotroph of the diploid yeast ''Saccharomyces cerevisiae'' was grown under conditions in which thymidyate levels varied from excess to depletion.Eckardt F, Kunz BA, Haynes RH. Variation of mutation and recombination frequencies over a range of thymidylate concentrations in a diploid thymidylate auxotroph. Curr Genet. 1983 Sep;7(5):399-402. doi: 10.1007/BF00445881. PMID: 24173422 High levels of thymidylate were observed to be mutagenic and recombinogenic, whereas starvation for thymidylate was recombinogenic but only slightly mutagenic.

References

External links

* http://money.cnn.com/magazines/fortune/fortune_archive/1990/11/05/74308/index.htm {{Nucleobases, nucleosides, and nucleotides Nucleosides Pyrimidinediones Hydroxymethyl compounds