7-Methylguanine

Last updated
7-Methylguanine
7methylguanine.png
Names
IUPAC name
7-Methylguanine
Preferred IUPAC name
2-Amino-7-methyl-1,7-dihydro-6H-purin-6-one
Other names
N7-Methylguanine; Epiguanine
Identifiers
3D model (JSmol)
174245
ChEBI
ChemSpider
ECHA InfoCard 100.008.575 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 209-431-0
KEGG
PubChem CID
UNII
  • InChI=1S/C6H7N5O/c1-11-2-8-4-3(11)5(12)10-6(7)9-4/h2H,1H3,(H3,7,9,10,12)
    Key: FZWGECJQACGGTI-UHFFFAOYSA-N
  • CN1C=NC2=C1C(=O)N=C(N2)N
Properties
C6H7N5O
Molar mass 165.156 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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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. However, the free 7-methylguanine base is not involved in the synthesis of nucleotides and not incorporated directly into nucleic acids. [1] [2] 7-Methylguanine is a natural inhibitor of poly (ADP-ribose) polymerase (PARP) and tRNA guanine transglycosylase (TGT) - and thus may exert anticancer activity. [3] [4] [5] For example, it was demonstrated that 7-methylguanine could accelerate apoptotic death of BRCA1-deficient breast cancer cells induced by cisplatin and doxorubicin. [6]

Related Research Articles

<span class="mw-page-title-main">Nucleotide base</span> Nitrogen-containing biological compounds that form nucleosides

Nucleotide 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. They function as the fundamental units of the genetic code, with the bases A, G, C, and T being found in DNA while A, G, C, and U are found in RNA. Thymine and uracil are distinguished by merely the presence or absence of a methyl group on the fifth carbon (C5) of these heterocyclic six-membered rings. In addition, some viruses have aminoadenine (Z) instead of adenine. It differs in having an extra amine group, creating a more stable bond to thymine.

<span class="mw-page-title-main">Ribonucleotide</span> Nucleotide containing ribose as its pentose component

In biochemistry, a ribonucleotide is a nucleotide containing ribose as its pentose component. It is considered a molecular precursor of nucleic acids. Nucleotides are the basic building blocks of DNA and RNA. Ribonucleotides themselves are basic monomeric building blocks for RNA. Deoxyribonucleotides, formed by reducing ribonucleotides with the enzyme ribonucleotide reductase (RNR), are essential building blocks for DNA. There are several differences between DNA deoxyribonucleotides and RNA ribonucleotides. Successive nucleotides are linked together via phosphodiester bonds.

Polyadenylation is the addition of a poly(A) tail to an RNA transcript, typically a messenger RNA (mRNA). The poly(A) tail consists of multiple adenosine monophosphates; in other words, it is a stretch of RNA that has only adenine bases. In eukaryotes, polyadenylation is part of the process that produces mature mRNA for translation. In many bacteria, the poly(A) tail promotes degradation of the mRNA. It, therefore, forms part of the larger process of gene expression.

A nucleoside triphosphate is a nucleoside containing a nitrogenous base bound to a 5-carbon sugar, 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.

<span class="mw-page-title-main">Poly (ADP-ribose) polymerase</span> Family of proteins

Poly (ADP-ribose) polymerase (PARP) is a family of proteins involved in a number of cellular processes such as DNA repair, genomic stability, and programmed cell death.

<span class="mw-page-title-main">Post-transcriptional modification</span> RNA processing within a biological cell

Transcriptional modification or co-transcriptional modification is a set of biological processes common to most eukaryotic cells by which an RNA primary transcript is chemically altered following transcription from a gene to produce a mature, functional RNA molecule that can then leave the nucleus and perform any of a variety of different functions in the cell. There are many types of post-transcriptional modifications achieved through a diverse class of molecular mechanisms.

<span class="mw-page-title-main">Adenosine diphosphate ribose</span> Chemical compound

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.

Purine metabolism refers to the metabolic pathways to synthesize and break down purines that are present in many organisms.

<span class="mw-page-title-main">ADP-ribosylation</span> Addition of one or more ADP-ribose moieties to a protein.

ADP-ribosylation is the addition of one or more ADP-ribose moieties to a protein. It is a reversible post-translational modification that is involved in many cellular processes, including cell signaling, DNA repair, gene regulation and apoptosis. Improper ADP-ribosylation has been implicated in some forms of cancer. It is also the basis for the toxicity of bacterial compounds such as cholera toxin, diphtheria toxin, and others.

In enzymology, a tRNA (guanine-N1-)-methyltransferase (EC 2.1.1.31) is an enzyme that catalyzes the chemical reaction

In enzymology, a tRNA (guanine-N2-)-methyltransferase (EC 2.1.1.32) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">PARP1</span> Mammalian protein found in Homo sapiens

Poly [ADP-ribose] polymerase 1 (PARP-1) also known as NAD+ ADP-ribosyltransferase 1 or poly[ADP-ribose] synthase 1 is an enzyme that in humans is encoded by the PARP1 gene. It is the most abundant of the PARP family of enzymes, accounting for 90% of the NAD+ used by the family. PARP1 is mostly present in cell nucleus, but cytosolic fraction of this protein was also reported.

<span class="mw-page-title-main">Tankyrase</span> Enzyme

Tankyrase, also known as tankyrase 1, is an enzyme that in humans is encoded by the TNKS gene. It inhibits the binding of TERF1 to telomeric DNA. Tankyrase attracts substantial interest in cancer research through its interaction with AXIN1 and AXIN2, which are negative regulators of pro-oncogenic β-catenin signaling. Importantly, activity in the β-catenin destruction complex can be increased by tankyrase inhibitors and thus such inhibitors are a potential therapeutic option to reduce the growth of β-catenin-dependent cancers.

<span class="mw-page-title-main">PARP4</span> Enzyme

Poly [ADP-ribose] polymerase 4 is an enzyme that in humans is encoded by the PARP4 gene.

<span class="mw-page-title-main">PARP2</span> Protein-coding gene in the species Homo sapiens

Poly [ADP-ribose] polymerase 2 is an enzyme that in humans is encoded by the PARP2 gene. It is one of the PARP family of enzymes.

<span class="mw-page-title-main">PARP10</span> Protein-coding gene in the species Homo sapiens

Poly [ADP-ribose] polymerase 10 is an enzyme that in humans is encoded by the PARP10 gene.

<span class="mw-page-title-main">DNA polymerase alpha subunit 2</span> Class of enzymes

DNA polymerase alpha subunit 2 is an enzyme that in humans is encoded by the POLA2 gene.

<span class="mw-page-title-main">DNA polymerase alpha catalytic subunit</span> Class of enzymes

DNA polymerase alpha catalytic subunit is an enzyme that in humans is encoded by the POLA1 gene.

Parthanatos is a form of programmed cell death that is distinct from other cell death processes such as necrosis and apoptosis. While necrosis is caused by acute cell injury resulting in traumatic cell death and apoptosis is a highly controlled process signalled by apoptotic intracellular signals, parthanatos is caused by the accumulation of Poly(ADP ribose) (PAR) and the nuclear translocation of apoptosis-inducing factor (AIF) from mitochondria. Parthanatos is also known as PARP-1 dependent cell death. PARP-1 mediates parthanatos when it is over-activated in response to extreme genomic stress and synthesizes PAR which causes nuclear translocation of AIF. Parthanatos is involved in diseases that afflict hundreds of millions of people worldwide. Well known diseases involving parthanatos include Parkinson's disease, stroke, heart attack, and diabetes. It also has potential use as a treatment for ameliorating disease and various medical conditions such as diabetes and obesity.

Ted M. Dawson is an American neurologist and neuroscientist. He is the Leonard and Madlyn Abramson Professor in Neurodegenerative Diseases and director of the Institute for Cell Engineering at Johns Hopkins University School of Medicine. He has joint appointments in the Department of Neurology, Neuroscience and Department of Pharmacology and Molecular Sciences.

References

  1. Craddock, VM; Mattocks, AR; Magee, PN (1968). "The fate of 7[14C]-methylguanine after administration to the rat". Biochem. J. 109 (1): 75–78. doi:10.1042/bj1090075. PMC   1186754 . PMID   5669851.
  2. Kaina, B; Heindorff, K; Aurich, O (1983). "O6-methylguanine, but not N7-methylguanine or N3-methyladenine, induces gene mutations, sister-chromatid exchanges and chromosomal aberrations in Chinese hamster cells". Mutat. Res. 108 (1–3): 279–292. doi:10.1016/0027-5107(83)90126-4. PMID   6835224.
  3. Nilov, D; Maluchenko, N; Kurgina, T; Pushkarev, S; Lys, A; Kutuzov, M; Gerasimova, N; Feofanov, A; Švedas, V; Lavrik, O; Studitsky, VM (2020). "Inhibition of poly(ADP-ribose) polymerase by nucleic acid metabolite 7-methylguanine". Int. J. Mol. Sci. 21 (6): 2159. doi: 10.3390/ijms21062159 . PMC   7139824 . PMID   32245127.
  4. Manasaryan, G; Suplatov, D; Pushkarev, S; Drobot, V; Kuimov, A; Švedas, V; Nilov, D (2021). "Bioinformatic analysis of the nicotinamide binding site in poly(ADP-ribose) polymerase family proteins". Cancers. 13 (6): 1201. doi: 10.3390/cancers13061201 . PMC   8002165 . PMID   33801950.
  5. Farkas, WR; Jacobson, KB; Katze, JR (1984). "Substrate and inhibitor specificity of tRNA-guanine ribosyltransferase". Biochim. Biophys. Acta. 781 (1–2): 64–75. doi:10.1016/0167-4781(84)90124-6. PMID   6696916.
  6. Nilov, DK; Tararov, VI; Kulikov, AV; Zakharenko, AL; Gushchina, IV; Mikhailov, SN; Lavrik, OI; Švedas, VK (2016). "Inhibition of poly(ADP-ribose) polymerase by nucleic acid metabolite 7-methylguanine". Acta Naturae. 8 (2): 108–115. doi:10.32607/20758251-2016-8-2-108-115. PMC   4947994 . PMID   27437145.