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Tumour mutational burden (abbreviated as TMB) is a genetic characteristic of tumorous tissue that can be informative to cancer research and treatment. It is defined as the number of non-inherited mutations per million bases (Mb) of investigated genomic sequence, and its measurement has been enabled by next generation sequencing. TMB has shown potential as a predictive biomarker with several applications, including associations reported between different TMB levels and patient response to immune checkpoint inhibitor (ICI) therapy in a variety of cancers
Tumor mutational burden
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V600E is a mutation of the BRAF gene in which valine (V) is substituted by glutamic acid (E) at amino acid 600. It is a driver mutation in a proportion of certain diagnoses, including melanoma, hairy cell leukemia, papillary thyroid carcinoma, colorectal cancer, non-small-cell lung cancer, Langerhans cell histiocytosis, Erdheim–Chester disease (a non-Langerhans-cell histiocytosis) and ameloblastoma. The mechanism of the mutation is that the negative charge of the acidic glutamic acid residue causes it to be phosphomimetic
V600E
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Worm bagging (also referred to as facultative vivipary or endotokia matricida) is a form of vivipary observed in nematodes, namely Caenorhabditis elegans. The process is characterized by eggs hatching within the parent and the larvae proceeding to consume and emerge from the parent. History While the phenomenon was mentioned as a result of fluorodeoxyuridine treatment as early as 1979 and egg-laying mutants were identified in 1984, the natural circumstances and mechanisms resulting in this behavior were not fully explored until 2003
Worm bagging
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Nucleobases (nitrogenous bases or simply bases) are nitrogen-containing biological compounds that form nucleosides, which, in turn, are components of nucleotides, with all of these monomers constituting the basic building blocks of nucleic acids. The ability of nucleobases to form base pairs and to stack one upon another leads directly to long-chain helical structures such as ribonucleic acid (RNA) and deoxyribonucleic acid (DNA). Five nucleobases—adenine (A), cytosine (C), guanine (G), thymine (T), and uracil (U)—are called primary or canonical
Nucleobase
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Nucleic acid analogues are compounds which are analogous (structurally similar) 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 phosphate backbone, a pentose sugar, either ribose or deoxyribose, and one of four nucleobases. An analogue may have any of these altered
Nucleic acid analogue
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Adenine () (symbol A or Ade) is a purine nucleobase. It is one of the four nucleobases in the nucleic acids of DNA, the other three being guanine (G), cytosine (C), and thymine (T). Adenine derivatives have various roles in biochemistry including cellular respiration, in the form of both the energy-rich adenosine triphosphate (ATP) and the cofactors nicotinamide adenine dinucleotide (NAD), flavin adenine dinucleotide (FAD) and Coenzyme A
Adenine
406
A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA and RNA. Dictated by specific hydrogen bonding patterns, "Watson–Crick" (or "Watson–Crick–Franklin") base pairs (guanine–cytosine and adenine–thymine) allow the DNA helix to maintain a regular helical structure that is subtly dependent on its nucleotide sequence
Base pair
407
5-Bromouracil (5-BrU, 5BrUra, or br5Ura) is a brominated derivative of uracil that acts as an antimetabolite or base analog, substituting for thymine in DNA, and can induce DNA mutation in the same way as 2-aminopurine. It is used mainly as an experimental mutagen, but its deoxyriboside derivative (5-bromo-2-deoxy-uridine) is used to treat neoplasms. 5-BrU exists in three tautomeric forms that have different base pairing properties
5-Bromouracil
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Cytosine () (symbol C or Cyt) is one of the four nucleobases found in DNA and RNA, along with adenine, guanine, and thymine (uracil in RNA). It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached (an amine group at position 4 and a keto group at position 2). The nucleoside of cytosine is cytidine
Cytosine
409
2,6-diaminopurine (2,6-DAP, also known as 2-aminoadenine) is a compound once used in the treatment of leukemia. As the Z base, it is found instead of adenine (A) in the genetic material of some bacteriophage viruses. In August 2011, a report, based on NASA studies with meteorites found on Earth, was published suggesting 2,6-diaminopurine and related organic molecules, including the DNA and RNA components adenine and guanine, may have been formed extraterrestrially in outer space
2,6-Diaminopurine
410
Flucytosine, also known as 5-fluorocytosine (5-FC), is an antifungal medication. It is specifically used, together with amphotericin B, for serious Candida infections and cryptococcosis. It may be used by itself or with other antifungals for chromomycosis
Flucytosine
411
Fluorouracil (5-FU, 5-fluorouracil), sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal cancer, stomach cancer, pancreatic cancer, breast cancer, and cervical cancer. As a cream it is used for actinic keratosis, basal cell carcinoma, and skin warts
Fluorouracil
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Guanine () (symbol G or Gua) is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine (uracil in RNA). In DNA, guanine is paired with cytosine. The guanine nucleoside is called guanosine
Guanine
413
5-Formylcytosine (5fC) is a pyrimidine nitrogen base derived from cytosine. In the context of nucleic acid chemistry and biology, it is regarded as an epigenetic marker. Discovered in 2011 in mammalian embryonic stem cells by Thomas Carell's research group the modified nucleoside was more recently confirmed to be relevant both as an intermediate in the active demethylation pathway and as a standalone epigenetic marker
5-Formylcytosine
414
5-Hydroxymethylcytosine (5hmC) is a DNA pyrimidine nitrogen base derived from cytosine. It is potentially important in epigenetics, because the hydroxymethyl group on the cytosine can possibly switch a gene on and off. It was first seen in bacteriophages in 1952
5-Hydroxymethylcytosine
415
Hypoxanthine is a naturally occurring purine derivative. It is occasionally found as a constituent of nucleic acids, where it is present in the anticodon of tRNA in the form of its nucleoside inosine. It has a tautomer known as 6-hydroxypurine
Hypoxanthine
416
Isocytosine or 2-aminouracil is a pyrimidine base that is an isomer of cytosine. It is used in combination with isoguanine in studies of unnatural nucleic acid analogues of the normal base pairs in DNA. In particular, it is used as a nucleobase of hachimoji RNA
Isocytosine
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Isoguanine or 2-hydroxyadenine is a purine base that is an isomer of guanine. It is a product of oxidative damage to DNA and has been shown to cause mutation. It is also used in combination with isocytosine in studies of unnatural nucleic acid analogues of the normal base pairs in DNA
Isoguanine
418
1-Methylcytosine is a methylated form of the DNA base cytosine. In 1-methylcytosine, a methyl group is attached to the 1st atom in the 6-atom ring. This methyl group distinguishes 1-methylcytosine from cytosine
1-Methylcytosine
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5-Methylcytosine is a methylated form of the DNA base cytosine (C) that regulates gene transcription and takes several other biological roles. When cytosine is methylated, the DNA maintains the same sequence, but the expression of methylated genes can be altered (the study of this is part of the field of epigenetics). 5-Methylcytosine is incorporated in the nucleoside 5-methylcytidine
5-Methylcytosine
420
6-O-Methylguanine is a derivative of the nucleobase guanine in which a methyl group is attached to the oxygen atom. It base-pairs to thymine rather than cytosine, causing a G:C to A:T transition in DNA. Formation 6-O-Methylguanine is formed in DNA by alkylation of the oxygen atom of guanine, most often by N-nitroso compounds (NOC) and sometimes due to methylation by other compounds such as endogenous S-adenosyl methionine
6-O-Methylguanine
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7-Methylguanine is a modified purine nucleobase. It is a methylated version of guanine. The 7-methylguanine nucleoside is called 7-methylguanosine
7-Methylguanine
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Methylthiouracil is an organosulfur compound that is used antithyroid preparation. It is a thioamide, closely related to propylthiouracil. Methylthiouracil is not used clinically in the United States, it has a similar mechanism of action and side effect to that of propylthiouricil
Methylthiouracil
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Propylthiouracil (PTU) is a medication used to treat hyperthyroidism. This includes hyperthyroidism due to Graves' disease and toxic multinodular goiter. In a thyrotoxic crisis it is generally more effective than methimazole
Propylthiouracil
424
Queuine () (Q) is a hypermodified nucleobase found in the first (or wobble) position of the anticodon of tRNAs specific for Asn, Asp, His, and Tyr, in most eukaryotes and prokaryotes. Because it is utilized by all eukaryotes but produced exclusively by bacteria, it is a putative vitamin. The nucleoside of queuine is queuosine
Queuine
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2-Thiouracil is a specific molecule consisting of a sulfated uracil. Medical use The substance is a historically relevant anti-thyroid preparation. Astwood E
2-Thiouracil
426
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 nucleobase
Thymine
427
Tioguanine, also known as thioguanine or 6-thioguanine (6-TG) is a medication used to treat acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), and chronic myeloid leukemia (CML). Long-term use is not recommended. It is given by mouth
Tioguanine
428
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
Uracil
429
Nucleotides are organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules within all life-forms on Earth. Nucleotides are obtained in the diet and are also synthesized from common nutrients by the liver
Nucleotide
430
Adenosine 5′-tetraphosphate, Ap4 or ATPP is a nucleotide. It is produced from ATP and triphosphate (P3) through the action of acetyl—CoA synthetase. Acetyl—CoA synthetase also produces adenosine 5'-pentaphosphate through the reaction of ADP and tetraphosphate (P4)
Adenosine 5'-tetraphosphate
431
Adenosine diphosphate ribose (ADPR) is an ester molecule formed into chains by the enzyme poly ADP ribose polymerase. ADPR is created from cyclic ADP-ribose (cADPR) by the CD38 enzyme using nicotinamide adenine dinucleotide (NAD+) as a cofactor. ADPR binds to and activates the TRPM2 ion channel
Adenosine diphosphate ribose
432
Adenosine monophosphate (AMP), also known as 5'-adenylic acid, is a nucleotide. AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine. It is an ester of phosphoric acid and the nucleoside adenosine
Adenosine monophosphate
433
Adenosine diphosphate (ADP), also known as adenosine pyrophosphate (APP), is an important organic compound in metabolism and is essential to the flow of energy in living cells. ADP consists of three important structural components: a sugar backbone attached to adenine and two phosphate groups bonded to the 5 carbon atom of ribose. The diphosphate group of ADP is attached to the 5’ carbon of the sugar backbone, while the adenine attaches to the 1’ carbon
Adenosine diphosphate
434
Adenosine triphosphate (ATP) is an organic compound that provides energy to drive and support many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms of life, ATP is often referred to as the "molecular unit of currency" of intracellular energy transfer. When consumed in metabolic processes, it converts either to adenosine diphosphate (ADP) or to adenosine monophosphate (AMP)
Adenosine triphosphate
435
Adenosine thiamine triphosphate (AThTP), or thiaminylated adenosine triphosphate, is a natural thiamine adenine nucleotide. It was discovered in Escherichia coli where it may account for up to 15 - 20% of total thiamine under carbon starvation. AThTP also exists in eukaryotic organisms such as yeast, roots of higher plants and animal tissues, albeit at a much lower concentration
Adenosine thiamine triphosphate
436
5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) is an intermediate in the generation of inosine monophosphate. AICAR is an analog of adenosine monophosphate (AMP) that is capable of stimulating AMP-dependent protein kinase (AMPK) activity. The drug has also been shown as a potential treatment for diabetes by increasing the metabolic activity of tissues by changing the physical composition of muscle
AICA ribonucleotide
437
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. They are reactive with N-Hydroxysuccinimide ester group which helps attach a fluorescent dye to the primary amino group on the nucleotide
Aminoallyl nucleotide
438
5′-Phosphoribosyl-5-aminoimidazole (or aminoimidazole ribotide, AIR) is a biochemical intermediate in the formation of purine nucleotides via inosine-5-monophosphate, and hence is a building block for DNA and RNA. The vitamins thiamine and cobalamin also contain fragments derived from AIR. It is an intermediate in the adenine pathway and is synthesized from 5′-phosphoribosylformylglycinamidine by AIR synthetase
5-Aminoimidazole ribotide
439
Antagomirs, also known as anti-miRs, are a class of chemically engineered oligonucleotides designed to silence endogenous microRNAs (also known as miRNAs or miRs). Antagomirs are a kind of antisense oligonucleotide, as their sequence is complementary to their specific miRNA target. Their structure has modifications so as to make them more resistant to degradation
Antagomir
440
Diadenosine tetraphosphate or Ap4A is a putative alarmone, ubiquitous in nature being common to everything from bacteria to humans. It is made up of two adenosines joined together by a 5′-5′ linked chain of four phosphates. Adenosine polyphosphates are capable of inducing multiple physiological effects
Ap4A
441
A bridged nucleic acid (BNA) is a modified RNA nucleotide. They are sometimes also referred to as constrained or inaccessible RNA molecules. BNA monomers can contain a five-membered, six-membered or even a seven-membered bridged structure with a "fixed" C3'-endo sugar puckering
Bridged nucleic acid
442
Bucladesine is a cyclic nucleotide derivative which mimics the action of endogenous cAMP and is a phosphodiesterase inhibitor. Bucladesine is a cell permeable cAMP analog. The compound is used in a wide variety of research applications because it mimics cAMP and can induce normal physiological responses when added to cells in experimental conditions
Bucladesine
443
Cangrelor, sold under the brand name Kengreal among others, is a P2Y12 inhibitor FDA approved as of June 2015 as an antiplatelet drug for intravenous application. Some P2Y12 inhibitors are used clinically as effective inhibitors of adenosine diphosphate-mediated platelet activation and aggregation. Unlike clopidogrel (Plavix), which is a prodrug, cangrelor is an active drug not requiring metabolic conversion
Cangrelor
444
Citicoline (INN), also known as cytidine diphosphate-choline (CDP-Choline) or cytidine 5'-diphosphocholine is an intermediate in the generation of phosphatidylcholine from choline, a common biochemical process in cell membranes. Citicoline is naturally occurring in the cells of human and animal tissue, in particular the organs. Use as a dietary supplement Citicoline is available as a supplement in over 70 countries under a variety of brand names: Cebroton, Ceraxon, Cidilin, Citifar, Cognizin, Difosfocin, Hipercol, NeurAxon, Nicholin, Sinkron, Somazina, Synapsine, Startonyl, Trausan, Xerenoos, etc
Citicoline
445
Cyclic adenosine monophosphate (cAMP, cyclic AMP, or 3',5'-cyclic adenosine monophosphate) is a second messenger, or cellular signal occurring within cells, that is important in many biological processes. cAMP is a derivative of adenosine triphosphate (ATP) and used for intracellular signal transduction in many different organisms, conveying the cAMP-dependent pathway. History Earl Sutherland of Vanderbilt University won a Nobel Prize in Physiology or Medicine in 1971 "for his discoveries concerning the mechanisms of the action of hormones", especially epinephrine, via second messengers (such as cyclic adenosine monophosphate, cyclic AMP)
Cyclic adenosine monophosphate
446
Cyclic ADP Ribose, frequently abbreviated as cADPR, is a cyclic adenine nucleotide (like cAMP) with two phosphate groups present on 5' OH of the adenosine (like ADP), further connected to another ribose at the 5' position, which, in turn, closes the cycle by glycosidic bonding to the nitrogen 1 (N1) of the same adenine base (whose position N9 has the glycosidic bond to the other ribose). The N1-glycosidic bond to adenine is what distinguishes cADPR from ADP-ribose (ADPR), the non-cyclic analog. cADPR is produced from nicotinamide adenine dinucleotide (NAD+) by ADP-ribosyl cyclases (EC 3
Cyclic ADP-ribose
447
Cyclic di-AMP (also called c-di-AMP and c-di-adenosine monophosphate) is a second messenger used in signal transduction in bacteria and archaea. It is present in many Gram-positive bacteria, some Gram-negative species, and archaea of the phylum euryarchaeota. It is one of many ubiquitous nucleotide second messengers including cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), guanosine pentaphosphate ((p)ppGpp), and cyclic di-GMP (c-di-GMP)
Cyclic di-AMP
448
Cyclic di-GMP (also called cyclic diguanylate and c-di-GMP) is a second messenger used in signal transduction in a wide variety of bacteria. Cyclic di-GMP is not known to be used by archaea, and has only been observed in eukaryotes in Dictyostelium. The biological role of cyclic di-GMP was first uncovered when it was identified as an allosteric activator of a cellulose synthase found in Gluconacetobacter xylinus in order to produce microbial cellulose
Cyclic di-GMP
449
Cyclic guanosine monophosphate–adenosine monophosphate (cyclic GMP-AMP, cGAMP) is the first cyclic di-nucleotide found in metazoa. In mammalian cells, cGAMP is synthesized by cyclic GMP-AMP synthase (cGAS) from ATP and GTP upon cytosolic DNA stimulation. cGAMP produced by cGAS contains mixed phosphodiester linkages, with one between 2'-OH of GMP and 5'-phosphate of AMP and the other between 3'-OH of AMP and 5'-phosphate of GMP
Cyclic guanosine monophosphate–adenosine monophosphate
450
Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). cGMP acts as a second messenger much like cyclic AMP. Its most likely mechanism of action is activation of intracellular protein kinases in response to the binding of membrane-impermeable peptide hormones to the external cell surface
Cyclic guanosine monophosphate
451
A cyclic nucleotide (cNMP) is a single-phosphate nucleotide with a cyclic bond arrangement between the sugar and phosphate groups. Like other nucleotides, cyclic nucleotides are composed of three functional groups: a sugar, a nitrogenous base, and a single phosphate group. As can be seen in the cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) images, the 'cyclic' portion consists of two bonds between the phosphate group and the 3' and 5' hydroxyl groups of the sugar, very often a ribose
Cyclic nucleotide
452
Cytidine monophosphate, also known as 5'-cytidylic acid or simply cytidylate, and abbreviated CMP, is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid with the nucleoside cytidine. CMP consists of the phosphate group, the pentose sugar ribose, and the nucleobase cytosine; hence, a ribonucleoside monophosphate
Cytidine monophosphate
453
Cytidine triphosphate (CTP) is a pyrimidine nucleoside triphosphate. CTP, much like ATP, consists of a ribose sugar, and three phosphate groups. The major difference between the two molecules is the base used, which in CTP is cytosine
Cytidine triphosphate
454
Denufosol (INN) is an inhaled drug for the treatment of cystic fibrosis, being developed by Inspire Pharmaceuticals and sponsored by the Cystic Fibrosis Foundation. It was tested in two Phase III clinical trials, TIGER-1 and TIGER-2. Initially, in the first Phase III trial, TIGER-1, the compound showed significant results as compared with placebo
Denufosol
455
Deoxyadenosine monophosphate (dAMP), also known as deoxyadenylic acid or deoxyadenylate in its conjugate acid and conjugate base forms, respectively, is a derivative of the common nucleic acid AMP, or adenosine monophosphate, in which the -OH (hydroxyl) group on the 2' carbon on the nucleotide's pentose has been reduced to just a hydrogen atom (hence the "deoxy-" part of the name). Deoxyadenosine monophosphate is abbreviated dAMP. It is a monomer used in DNA
Deoxyadenosine monophosphate
456
Deoxyadenosine triphosphate (dATP) is a nucleotide used in cells for DNA synthesis (or replication), as a substrate of DNA polymerase. Deoxyadenosine triphosphate is produced from DNA by the action of nuclease P1, adenylate kinase, and pyruvate kinase. Health effects High levels of dATP can be toxic and result in impaired immune function, since dATP acts as a noncompetitive inhibitor for the DNA synthesis enzyme ribonucleotide reductase
Deoxyadenosine triphosphate
457
Deoxycytidine diphosphate is a nucleoside diphosphate. It is related to the common nucleic acid CTP, or cytidine triphosphate, with the -OH (hydroxyl) group on the 2' carbon on the nucleotide's pentose removed (hence the deoxy- part of the name), and with one fewer phosphoryl group than CTP . 2'-deoxycytidine diphosphate is abbreviated as dCDP
Deoxycytidine diphosphate
458
Deoxycytidine triphosphate (dCTP) is a nucleoside triphosphate that contains the pyrimidine base cytosine. The triphosphate group contains high-energy phosphoanhydride bonds, which liberate energy when hydrolized. DNA polymerase enzymes use this energy to incorporate deoxycytidine into a newly synthesized strand of DNA
Deoxycytidine triphosphate
459
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 nitrogenous base, and one phosphoryl group
Deoxyribonucleotide
460
Deoxyuridine monophosphate (dUMP), also known as deoxyuridylic acid or deoxyuridylate in its conjugate acid and conjugate base forms, respectively, is a deoxynucleotide. It is an intermediate in the metabolism of deoxyribonucleotides. Biosynthesis Deoxyuridine monophosphate (dUMP) is the deoxygenated form of uridine monophosphate (UMP), and is the precursor to deoxythymidine monophosphate (dTMP), a component of DNA nucleotide biosynthesis
Deoxyuridine monophosphate
461
Dideoxynucleotides are chain-elongating inhibitors of DNA polymerase, used in the Sanger method for DNA sequencing. They are also known as 2',3' because both the 2' and 3' positions on the ribose lack hydroxyl groups, and are abbreviated as ddNTPs (ddGTP, ddATP, ddTTP and ddCTP). Role in the Sanger method The Sanger method is used to amplify a target segment of DNA, so that the DNA sequence can be determined precisely
Dideoxynucleotide
462
Disodium guanylate, also known as sodium 5'-guanylate and disodium 5'-guanylate, is a natural sodium salt of the flavor enhancing nucleotide guanosine monophosphate (GMP). Disodium guanylate is a food additive with the E number E627. It is commonly used in conjunction with glutamic acid
Disodium guanylate
463
Disodium inosinate (E631) is the disodium salt of inosinic acid with the chemical formula C10H11N4Na2O8P. It is used as a food additive and often found in instant noodles, potato chips, and a variety of other snacks. Commercial disodium inosinate may either be obtained from bacterial fermentation of sugars or prepared from animal products
Disodium inosinate
464
In biochemistry, flavin adenine dinucleotide (FAD) is a redox-active coenzyme associated with various proteins, which is involved with several enzymatic reactions in metabolism. A flavoprotein is a protein that contains a flavin group, which may be in the form of FAD or flavin mononucleotide (FMN). Many flavoproteins are known: components of the succinate dehydrogenase complex, α-ketoglutarate dehydrogenase, and a component of the pyruvate dehydrogenase complex
Flavin adenine dinucleotide
465
GC skew is when the nucleotides guanine and cytosine are over- or under-abundant in a particular region of DNA or RNA. GC skew is also a statistical method for measuring strand-specific guanine overrepresentation. In equilibrium conditions (without mutational or selective pressure and with nucleotides randomly distributed within the genome) there is an equal frequency of the four DNA bases (adenine, guanine, thymine, and cytosine) on both single strands of a DNA molecule
GC skew
466
Glycineamide ribonucleotide (or GAR) is a biochemical intermediate in the formation of purine nucleotides via inosine-5-monophosphate, and hence is a building block for DNA and RNA. The vitamins thiamine and cobalamin also contain fragments derived from GAR. GAR is the product of the enzyme phosphoribosylamine—glycine ligase acting on phosphoribosylamine (PRA) to combine it with glycine in a process driven by ATP
Glycineamide ribonucleotide
467
GTPgammaS (GTPγS, guanosine 5'-O-[gamma-thio]triphosphate) is a non-hydrolyzable or slowly hydrolyzable G-protein-activating analog of guanosine triphosphate (GTP). Many GTP binding proteins demonstrate activity when bound to GTP, and are inactivated via the hydrolysis of the phosphoanhydride bond that links the γ-phosphate to the remainder of the nucleotide, leaving a bound guanosine diphosphate (GDP) and releasing an inorganic phosphate. This usually occurs rapidly, and the GTP-binding protein can then only be activated by exchanging the GDP for a new GTP molecule
GTPgammaS
468
Guanosine diphosphate mannose or GDP-mannose is a nucleotide sugar that is a substrate for glycosyltransferase reactions in metabolism. This compound is a substrate for enzymes called mannosyltransferases. Known as donor of activated mannose in all glycolytic reactions, GDP-mannose is essential in eukaryotes
Guanosine diphosphate mannose
469
(p)ppGpp, guanosine pentaphosphate and tetraphosphate, also known as the "magic spot" nucleotides, are alarmones involved in the stringent response in bacteria that cause the inhibition of RNA synthesis when there is a shortage of amino acids. This inhibition by (p)ppGpp decreases translation in the cell, conserving amino acids present. Furthermore, ppGpp and pppGpp cause the up-regulation of many other genes involved in stress response such as the genes for amino acid uptake (from surrounding media) and biosynthesis
Guanosine pentaphosphate
470
Guanosine monophosphate (GMP), also known as 5′-guanidylic acid or guanylic acid (conjugate base guanylate), is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid with the nucleoside guanosine. GMP consists of the phosphate group, the pentose sugar ribose, and the nucleobase guanine; hence it is a ribonucleoside monophosphate
Guanosine monophosphate
471
Guanosine diphosphate, abbreviated GDP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside guanosine. GDP consists of a pyrophosphate group, a pentose sugar ribose, and the nucleobase guanine
Guanosine diphosphate
472
Guanosine-5'-triphosphate (GTP) is a purine nucleoside triphosphate. It is one of the building blocks needed for the synthesis of RNA during the transcription process. Its structure is similar to that of the guanosine nucleoside, the only difference being that nucleotides like GTP have phosphates on their ribose sugar
Guanosine triphosphate
473
5'-Guanylyl imidodiphosphate (GDPNP) is a purine nucleotide. It is an analog of guanosine triphosphate in which one of the oxygen atoms is replaced with an amine, producing a non-hydrolyzable functional group. Guanylyl imidodiphosphate binds tightly to G-proteins in the presence of Mg2+
5'-Guanylyl imidodiphosphate
474
Hovlinc RNA is a self-cleaving ribozyme of about 168 nucleotides found in a very long noncoding RNA (vlincRNA) in humans, chimpanzees, and gorillas. The word "hovlinc" comes from "hominin vlincRNA-located" RNA. Hovlinc is only a fourth known case of a ribozyme in human
Hovlinc
475
Inosine triphosphate (ITP) is an intermediate in the purine metabolism pathway, seen in the synthesis of ATP and GTP. It comprises an inosine nucleotide containing three phosphate groups esterified to the sugar moiety. ITP results from deamination of ATP
Inosine triphosphate
476
Inosinic acid or inosine monophosphate (IMP) is a nucleotide (that is, a nucleoside monophosphate). Widely used as a flavor enhancer, it is typically obtained from chicken byproducts or other meat industry waste. Inosinic acid is important in metabolism
Inosinic acid
477
An internal ribosome entry site, abbreviated IRES, is an RNA element that allows for translation initiation in a cap-independent manner, as part of the greater process of protein synthesis. In eukaryotic translation, initiation typically occurs at the 5' end of mRNA molecules, since 5' cap recognition is required for the assembly of the initiation complex. The location for IRES elements is often in the 5'UTR, but can also occur elsewhere in mRNAs
Internal ribosome entry site
478
Klee diagrams, named for their resemblance to paintings by Paul Klee, are false-colour maps that represent a way of assembling and viewing large genomic datasets. Contemporary research has produced genomic databases for an enormous range of life forms, inviting insights into the genetic basis of biodiversity. Indicator vectors are used to depict nucleotide sequences
Klee diagram
479
In molecular biology, the NAD+ five-prime cap (NAD+ 5’ cap) refers to a molecule of nicotinamide adenine dinucleotide (NAD+), a nucleoside-containing metabolite, covalently bonded the 5’ end of cellular mRNA. While the more common methylated guanosine (m7G) cap is added to RNA by a capping complex that associates with RNA polymerase II (RNAP II), the NAD cap is added during transcriptional initiation by the RNA polymerase itself, acting as a non-canonical initiating nucleotide (NCIN). As such, while m7G capping can only occur in organisms possessing specialized capping complexes, because NAD capping is performed by RNAP itself, it is hypothesized to occur in most, if not all, organisms
NAD+ Five-prime cap
480
5'-guanosyl-methylene-triphosphate (GDPCP) and 5'-adenosyl-methylene-triphosphate (ADPCP) are analogues of guanosine 5'-triphosphate (GTP) and adenosine 5'-triphosphate (ATP), which store chemical energy from metabolism in the cell. Hydrolysis of nucleoside triphosphates (NTPs) such as ATP and GTP yields energy, inorganic phosphate (Pi or PPi), and either NDP or NMP. GDPCP and ADPCP are not subject to hydrolysis under the same conditions as NTPs; it is this property which makes them useful in experiments in biochemistry and molecular biology
NDPCP
481
Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine nucleobase and the other, nicotinamide
Nicotinamide adenine dinucleotide
482
Nicotinamide adenine dinucleotide phosphate, abbreviated NADP+ or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require NADPH as a reducing agent ('hydrogen source'). NADPH is the reduced form of NADP+, the oxidized form. NADP+ is used by all forms of cellular life
Nicotinamide adenine dinucleotide phosphate
483
Nicotinamide mononucleotide (“NMN” and “β-NMN”) is a nucleotide derived from ribose, nicotinamide, nicotinamide riboside and niacin. In humans, several enzymes use NMN to generate nicotinamide adenine dinucleotide (NADH). In mice, it has been proposed that NMN is absorbed via the small intestine within 10 minutes of oral uptake and converted to nicotinamide adenine dinucleotide (NAD+) through the Slc12a8 transporter
Nicotinamide mononucleotide
484
Nicotinic acid adenine dinucleotide phosphate, (NAADP), is a Ca2+-mobilizing second messenger synthesised in response to extracellular stimuli. Like its mechanistic cousins, IP3 and cyclic adenosine diphosphoribose (Cyclic ADP-ribose), NAADP binds to and opens Ca2+ channels on intracellular organelles, thereby increasing the intracellular Ca2+ concentration which, in turn, modulates sundry cellular processes (see Calcium signalling). Structurally, it is a dinucleotide that only differs from the house-keeping enzyme cofactor, NADP by a hydroxyl group (replacing the nicotinamide amino group) and yet this minor modification converts it into the most potent Ca2+-mobilizing second messenger yet described
Nicotinic acid adenine dinucleotide phosphate
485
An NTP binding site is a type of binding site found in nucleoside monophosphate (NMP) kinases, N can be adenosine or guanosine. A P-loop is one of the structural motifs common for nucleoside triphosphate (NTP) binding sites, it interacts with the bound nucleotide's phosphoryl groups. For the binding site to be able to bind a nucleotide, the nucleotide must be complex bound to Mg2+ or Mn2+
NTP binding site
486
The nucleic acid notation currently in use was first formalized by the International Union of Pure and Applied Chemistry (IUPAC) in 1970. This universally accepted notation uses the Roman characters G, C, A, and T, to represent the four nucleotides commonly found in deoxyribonucleic acids (DNA). Given the rapidly expanding role for genetic sequencing, synthesis, and analysis in biology, some researchers have developed alternate notations to further support the analysis and manipulation of genetic data
Nucleic acid notation
487
A nucleoside triphosphate is a nucleoside containing a nitrogenous base bound to a 5-carbon sugar (either ribose or deoxyribose), with three phosphate groups bound to the sugar. They are the molecular precursors of both DNA and RNA, which are chains of nucleotides made through the processes of DNA replication and transcription. Nucleoside triphosphates also serve as a source of energy for cellular reactions and are involved in signalling pathways
Nucleoside triphosphate
488
A salvage pathway is a pathway in which a biological product is produced from intermediates in the degradative pathway of its own or a similar substance. The term often refers to nucleotide salvage in particular, in which nucleotides (purine and pyrimidine) are synthesized from intermediates in their degradative pathway. Nucleotide salvage pathways are used to recover bases and nucleosides that are formed during degradation of RNA and DNA
Nucleotide salvage
489
Nucleotide sugars are the activated forms of monosaccharides. Nucleotide sugars act as glycosyl donors in glycosylation reactions. Those reactions are catalyzed by a group of enzymes called glycosyltransferases
Nucleotide sugar
490
Nullomers are short sequences of DNA that do not occur in the genome of a species (for example, humans), even though they are theoretically possible. Nullomers must be under selective pressure - for example, they may be toxic to the cell. Some nullomers have been shown to be useful to treat leukemia, breast, and prostate cancer
Nullomers
491
3′-Phosphoadenosine-5′-phosphosulfate (PAPS) is a derivative of adenosine monophosphate (AMP) that is phosphorylated at the 3′ position and has a sulfate group attached to the 5′ phosphate. It is the most common coenzyme in sulfotransferase reactions and hence part of sulfation pathways. It is endogenously synthesized by organisms via the phosphorylation of adenosine 5′-phosphosulfate (APS), an intermediary metabolite
3'-Phosphoadenosine-5'-phosphosulfate
492
Phosphoribosyl-N-formylglycineamide (or FormylGlycinAmideRibotide, FGAR) is a biochemical intermediate in the formation of purine nucleotides via inosine-5-monophosphate, and hence is a building block for DNA and RNA. The vitamins thiamine and cobalamin also contain fragments derived from FGAR. FGAR is formed when the enzyme phosphoribosylglycinamide formyltransferase adds a formyl group from 10-formyltetrahydrofolate to glycineamide ribonucleotide (GAR) in reaction EC 2
Phosphoribosyl-N-formylglycineamide
493
A phosphorimidazolide is a chemical compound in which a phosphoryl mono-ester is covalently bound to a nitrogen atom in an imidazole ring. They are a type of phosphoramidate. These phosphorus (V) compounds are encountered as reagents used for making new phosphoanhydride bonds with phosphate mono-esters, and as reactive intermediates in phosphoryl transfer reactions in some enzyme-catalyzed transformations
Phosphorimidazolide
494
In molecular biology, a polynucleotide (from Ancient Greek πολυς (polys) 'many') is a biopolymer composed of 13 nucleotide monomers, covalently bonded in a chain. DNA (deoxyribonuc and RNA (ribonucleic acid) are examples of polynucleotides with distinct Sequence Although DNA and RNA do not generally occur in the same polynucleotide, the four species of nucleotides may occur in any order in the chain. The sequence of DNA or RNA species for a given polynucleotide is the main factor determining its function in a living organism or a scientific experiment
Polynucleotide
495
The Pseudo K-tuple nucleotide composition or PseKNC, was extended from Chou's Pseudo amino acid composition (PseAAC). Both PseAAC and PseKNC are of vector descriptor, but the former represents protein or peptide sequences while the latter represents DNA or RNA sequences. To avoid completely losing the sequence-order information for protein and peptide sequences, the PseAAC was proposed by Kuo-Chen Chou
Pseudo K-tuple nucleotide composition
496
In chemistry, pyrophosphates are phosphorus oxyanions that contain two phosphorus atoms in a P–O–P linkage. A number of pyrophosphate salts exist, such as disodium pyrophosphate (Na2H2P2O7) and tetrasodium pyrophosphate (Na4P2O7), among others. Often pyrophosphates are called diphosphates
Pyrophosphate
497
Remdesivir, sold under the brand name Veklury, is a broad-spectrum antiviral medication developed by the biopharmaceutical company Gilead Sciences. It is administered via injection into a vein. During the COVID‑19 pandemic, remdesivir was approved or authorized for emergency use to treat COVID‑19 in numerous countries
Remdesivir
498
Sugar phosphates (sugars that have added or substituted phosphate groups) are often used in biological systems to store or transfer energy. They also form the backbone for DNA and RNA. Sugar phosphate backbone geometry is altered in the vicinity of the modified nucleotides
Sugar phosphates
499
Thymidine diphosphate glucose (often abbreviated dTDP-glucose or TDP-glucose) is a nucleotide-linked sugar consisting of deoxythymidine diphosphate linked to glucose. It is the starting compound for the syntheses of many deoxysugars. Biosynthesis DTDP-glucose is produced by the enzyme glucose-1-phosphate thymidylyltransferase and is synthesized from dTTP and glucose-1-phosphate
Thymidine diphosphate glucose