メチル化剤

WordNet

a substance that exerts some force or effect
a businessman who buys or sells for another in exchange for a commission (同)factor, broker
any agent or representative of a federal agency or bureau (同)federal agent
a representative who acts on behalf of other persons or organizations
an active and efficient cause; capable of producing a certain effect; "their research uncovered new disease agents"
how long something has existed; "it was replaced because of its age"
a time of life (usually defined in years) at which some particular qualification or power arises; "she was now of school age"; "tall for his eld" (同)eld
begin to seem older; get older; "The death of his wife caused him to age fast"
make older; "The death of his child aged him tremendously"

PrepTutorEJDIC

『代理人』;周旋人 / 働き(作用)を起こすもの;作用物,薬剤 / (政府機関,特にFBI,CIAなどの)部員,機関員
〈U〉(一般に)『年齢』,寿命;〈C〉(個々の)『年齢』,年 / 〈U〉成年(おとなとしての資格・権利を得る年齢;通例18または21歳) / 〈U〉『老齢』;《集合的に》老人たち / 〈U〉(人生の)『一時期』;〈C〉世代(generation) / 〈U〉〈C〉《しばしばA-》(歴史上の)『時代』 / 〈C〉《話》長い間 / 年をとる,ふける;〈物が〉古くなる / 〈年〉'を'とらせる;〈物〉'を'古びさせる

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/04/27 21:24:59」(JST)

wiki en

In the chemical sciences, methylation denotes the addition of a methyl group on a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with a methyl group, rather than a larger carbon chain, replacing a hydrogen atom. These terms are commonly used in chemistry, biochemistry, soil science, and the biological sciences.

In biological systems, methylation is catalyzed by enzymes; such methylation can be involved in modification of heavy metals, regulation of gene expression, regulation of protein function, and RNA processing. Methylation of heavy metals can also occur outside biological systems. Chemical methylation of tissue samples is also one method for reducing certain histological staining artifacts. The counterpart of methylation is demethylation.

1 In biology
- 1.1 O-Methyltransferases
- 1.2 Methylcobalamin
- 1.3 DNA methylation
- 1.4 Protein methylation
2 In chemistry
- 2.1 Electrophilic methylation
- 2.2 Specialized methylation protocols
- 2.3 Nucleophilic methylation
3 5-O-methylations
4 See also
- 4.1 Biology topics
- 4.2 Organic chemistry topics
5 References
6 External links

In biology

O-Methyltransferases

A wide variety of phenols undergo O-methylation to give anisole derivatives. This process, catalyzed by enzymes such as caffeoyl-CoA O-methyltransferase, is a key reaction in the biosynthesis of lignols, precursors to lignin, a major structural component of plants.

One step in the biosynthesisof the lignol sinapyl alcohol is methylation.

Methylcobalamin

Methylcobalamin is an important methylating agent in nature.

The methylation reaction catalyzed by methionine synthase.

Methionine synthase catalyzes the final step in the regeneration of methionine(Met) from homocysteine(Hcy). The overall reaction transforms 5-methyltetrahydrofolate(N⁵-MeTHF) into tetrahydrofolate (THF) while transferring a methyl group to Hcy to form Met. In methylcobalamin-dependent forms of the enzyme, the reaction proceeds by two steps in a ping-pong reaction. The enzyme is initially primed into a reactive state by the transfer of a methyl group from N⁵-MeTHF to Co(I) in enzyme-bound cobalamin(Cob), forming methyl-cobalamin(Me-Cob) that now contains Me-Co(III) and activating the enzyme. Then, a Hcy that has coordinated to an enzyme-bound zinc to form a reactive thiolate reacts with the Me-Cob. The activated methyl group is transferred from Me-Cob to the Hcy thiolate, which regenerates Co(I) in cob, and Met is released from the enzyme.^[1]

DNA methylation

DNA methylation in vertebrates typically occurs at CpG sites (cytosine-phosphate-guanine sites, that is, where a cytosine is directly followed by a guanine in the DNA sequence). This methylation results in the conversion of the cytosine to 5-methylcytosine. The formation of Me-CpG is catalyzed by the enzyme DNA methyltransferase. Human DNA has about 80–90% of CpG sites methylated, but there are certain areas, known as CpG islands, that are GC-rich (high guanine and cytosine content, made up of about 65% CG residues), wherein none are methylated. These are associated with the promoters of 56% of mammalian genes, including all ubiquitously expressed genes. One to two percent of the human genome are CpG clusters, and there is an inverse relationship between CpG methylation and transcriptional activity.

Methylation contributing to epigenetic inheritance can occur through either DNA methylation or protein methylation.

Protein methylation

Protein methylation typically takes place on arginine or lysine amino acid residues in the protein sequence.^[2] Arginine can be methylated once (monomethylated arginine) or twice, with either both methyl groups on one terminal nitrogen (asymmetric dimethylarginine) or one on both nitrogens (symmetric dimethylarginine) by protein arginine methyltransferases (PRMTs). Lysine can be methylated once, twice or three times by lysine methyltransferases. Protein methylation has been most studied in the histones. The transfer of methyl groups from S-adenosyl methionine to histones is catalyzed by enzymes known as histone methyltransferases. Histones that are methylated on certain residues can act epigenetically to repress or activate gene expression.^[3]^[4] Protein methylation is one type of post-translational modification.

In chemistry

The term methylation in organic chemistry refers to the alkylation process used to describe the delivery of a CH₃ group.^[5]

Electrophilic methylation

Methylations are commonly performed using electrophilic methyl sources such as iodomethane,^[6] dimethyl sulfate,^[7]^[8] dimethyl carbonate,^[9] or tetramethylammonium chloride.^[10] Less common but with the more powerful (and more dangerous) methylating reagents include methyl triflate,^[11] diazomethane,^[12] and methyl fluorosulfonate (magic methyl). These reagents all react via S_N2 nucleophilic substitutions. For example a carboxylate may be methylated on oxygen to give a methyl ester, an alkoxide salt RO⁻ may be likewise methylated to give an ether, ROCH₃, or a ketone enolate may be methylated on carbon to produce a new ketone.

Specialized methylation protocols

The Eschweiler-Clarke reaction is a method for methylation of amines.^[13] This method avoids the risk of quaternization, which occurs when amines are methylated with methyl halides.

The Purdie methylation is a specific for the methylation at oxygen of carbohydrates using iodomethane and silver oxide.^[14]

Nucleophilic methylation

Methylation sometimes involve use of nucleophilic methyl reagents. Strongly nucleophilic methylating agents include methyllithium (CH₃Li)^[15] or Grignard reagents such as methylmagnesium bromide (CH₃MgX).^[16] For example, CH₃Li will add methyl groups to the carbonyl (C=O) of ketones and aldehyde.:

Milder methylating agents include tetramethyltin, dimethylzinc, and trimethylaluminium.^[17]

5-O-methylations

5-O-methylgenistein
5-O-methylmyricetin
5-O-methylquercetin, also known as azaleatin

References

^ Matthews, R. G.; Smith, A. E.; Zhou, Z. S.; Taurog, R. E.; Bandarian, V.; Evans, J. C.; Ludwig, M. (2003). "Cobalamin-Dependent and Cobalamin-Independent Methionine Synthases: Are There Two Solutions to the Same Chemical Problem?". Helvetica Chimica Acta 86 (12): 3939–3954. doi:10.1002/hlca.200390329.
^ Walsh, Christopher (2006). "Chapter 5 – Protein Methylation" (PDF). Posttranslational modification of proteins: expanding nature's inventory. Roberts and Co. Publishers. ISBN 0-9747077-3-2.
^ Grewal, S. I.; Rice, J. C. (2004). "Regulation of heterochromatin by histone methylation and small RNAs". Current Opinion in Cell Biology 16 (3): 230–238. doi:10.1016/j.ceb.2004.04.002. PMID 15145346.
^ Nakayama, J. -I.; Rice, J. C.; Strahl, B. D.; Allis, C. D.; Grewal, S. I. (2001). "Role of Histone H3 Lysine 9 Methylation in Epigenetic Control of Heterochromatin Assembly". Science 292 (5514): 110–113. doi:10.1126/science.1060118. PMID 11283354.
^ March, Jerry; Smith, Michael W (2001). March's advanced organic chemistry: reactions, mechanisms, and structure. New York: Wiley. ISBN 0-471-58589-0.
^ Vyas, G. N.; Shah, N. M. (1951). "Quninacetophenone monomethyl ether". Organic Syntheses 31: 90. doi:10.15227/orgsyn.031.0090.
^ Hiers, G. S. (1929). "Anisole". Organic Syntheses 9: 12. doi:10.15227/orgsyn.009.0012.
^ Icke, Roland N.; Redemann, Ernst; Wisegarver, Burnett B.; Alles, Gordon A. (1949). "m-Methoxybenzaldehyde". Organic Syntheses 29: 63. doi:10.15227/orgsyn.029.0063.
^ Tundo, Pietro; Selva, Maurizio; Bomben, Andrea (1999). "Mono-C-methylathion of arylacetonitriles and methyl arylacetates by dimethyl carbonate: a general method for the synthesis of pure 2-arylpropionic acids. 2-Phenylpropionic acid". Organic Syntheses 76: 169. doi:10.15227/orgsyn.076.0169.
^ Nenad, Maraš; Polanc, Slovenko; Kočevar, Marijan (2008). "Microwave-assisted methylation of phenols with tetramethylammonium chloride in the presence of K₂CO₃ or Cs₂CO₃". Tetrahedron 64 (51): 11618–11624. doi:10.1016/j.tet.2008.10.024.
^ Poon, Kevin W. C.; Albiniak, Philip A.; Dudley, Gregory B. (2007). "Protection of alcohols using 2-benzyloxy-1-methylpyridinium trifluoromethanesulfanonate: Methyl (R)-(-)-3-benzyloxy-2-methyl propanoate". Organic Syntheses 84: 295. doi:10.15227/orgsyn.084.0295.
^ Neeman, M.; Johnson, William S. (1961). "Cholestanyl methyl ether". Organic Syntheses 41: 9. doi:10.15227/orgsyn.041.0009.
^ Icke, Roland N.; Wisegarver, Burnett B.; Alles, Gordon A. (1945). "β-Phenylethyldimethylamine". Organic Syntheses 25: 89. doi:10.15227/orgsyn.025.0089.
^ Purdie, T.; Irvine, J. C. (1903). "C.?The alkylation of sugars". Journal of the Chemical Society, Transactions 83: 1021. doi:10.1039/CT9038301021.
^ Lipsky, Sharon D.; Hall, Stan S. (1976). "Aromatic Hydrocarbons from aromatic ketones and aldehydes: 1,1-Diphenylethane". Organic Syntheses 55: 7. doi:10.15227/orgsyn.055.0007.
^ Grummitt, Oliver; Becker, Ernest I. (1950). "trans-1-Phenyl-1,3-butadiene". Organic Syntheses 30: 75. doi:10.15227/orgsyn.030.0075.
^ Negishi, Ei-ichi; Matsushita, Hajime (1984). ""Palladium-Catalyzed Synthesis of 1,4-Dienes by Allylation of Alkenyalane: α-Farnesene". Organic Syntheses 62: 31. doi:10.15227/orgsyn.062.0031.
^ Wienken CJ, Baaske P, Duhr S, Braun D (2011). "Thermophoretic melting curves quantify the conformation and stability of RNA and DNA". Nucleic Acids Research 39 (8): e52–e52. doi:10.1093/nar/gkr035. PMC 3082908. PMID 21297115.

External links

deltaMasses Detection of Methylations after Mass Spectrometry

UpToDate Contents

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English Journal

Iridium-catalyzed selective α-methylation of ketones with methanol.

Ogawa S, Obora Y.Author information Department of Chemistry and Materials Engineering, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka 564-8680, Japan. obora@kansai-u.ac.jp.AbstractIridium-catalyzed selective α-dimethylation and α-methylation of ketones or phenylacetonitriles, using methanol as the methylating agent, were achieved. In addition, three-component cross α-methyl-alkylation was successfully performed using methyl ketones with methanol and primary alcohols with long-chain alkyl groups. This method provides a very convenient direct route to α-methylated ketones, using methanol.
Chemical communications (Cambridge, England).Chem Commun (Camb).2014 Mar 7;50(19):2491-3. doi: 10.1039/c3cc49626k. Epub 2014 Jan 23.
Iridium-catalyzed selective α-dimethylation and α-methylation of ketones or phenylacetonitriles, using methanol as the methylating agent, were achieved. In addition, three-component cross α-methyl-alkylation was successfully performed using methyl ketones with methanol and primary alcohols with l
PMID 24458143

In search of markers for somatic embryo maturation in hybrid larch (Larix × eurolepis): global DNA methylation and proteomic analyses.

Teyssier C, Maury S, Beaufour M, Grondin C, Delaunay A, Le Metté C, Ader K, Cadene M, Label P, Lelu-Walter MA.Author information INRA, UR 0588, Research Unit for Breeding, Genetics and Physiology of Forest Trees, Orléans, F-45075, France.AbstractA global DNA methylation and proteomics approach was used to investigate somatic embryo maturation in hybrid larch. Each developmental step during somatic embryogenesis was associated with a distinct and significantly different global DNA methylation level: from 45.8% mC for undifferentiated somatic embryos (1-week proliferation) to 61.5% mC for immature somatic embryos (1-week maturation), while maturation was associated with a decrease in DNA methylation to 53.4% for mature cotyledonary somatic embryos (8-weeks maturation). The presence of 5-azacytidine (hypo-methylating agent) or hydroxyurea (hyper-methylating agent) in the maturation medium altered the global DNA methylation status of the embryogenic cultures, and significantly reduced both their relative growth rate and embryogenic potential, suggesting an important role for DNA methylation in embryogenesis. Maturation was also assessed by examining changes in the total protein profile. Storage proteins, identified as legumin- and vicilin-like, appeared at the precotyledonary stage. In the proteomic study, total soluble proteins were extracted from embryos after 1 and 8 weeks of maturation, and separated by two-dimensional gel electrophoresis. There were 147 spots which showed significant differences between the stages of maturation; they were found to be involved mainly in primary metabolism and the stabilization of the resulting metabolites. This indicated that the somatic embryo was still metabolically active at 8 weeks of maturation. This is the first report of analyses of global DNA methylation (including the effects of hyper- and hypo-treatments) and proteome during somatic embryogenesis in hybrid larch, and thus provides novel insights into maturation of conifer somatic embryos.
Physiologia plantarum.Physiol Plant.2014 Feb;150(2):271-91. doi: 10.1111/ppl.12081. Epub 2013 Jul 31.
A global DNA methylation and proteomics approach was used to investigate somatic embryo maturation in hybrid larch. Each developmental step during somatic embryogenesis was associated with a distinct and significantly different global DNA methylation level: from 45.8% mC for undifferentiated somatic
PMID 23789891

Epigenetic biomarkers of colorectal cancer: Focus on DNA methylation.

Coppedè F.Author information Department (DAI) of Neuroscience, Pisa University Hospital (AOUP), Italy; Faculty of Medicine, University of Pisa, Italy. Electronic address: f.coppede@geog.unipi.it.AbstractThe original theory of the multi-step process of colorectal cancer (CRC), suggesting that the disease resulted from the accumulation of mutations in oncogenes and tumor suppressor genes in colonic mucosa cells, has been largely revised following the observation that epigenetic modifications of several genes occur in the average CRC genome. Therefore, the current opinion is that CRCs are the consequence of the accumulation of both mutations and epigenetic modifications of several genes. This mini-review article focuses on DNA methylation biomarkers in CRC. Recent large-scale DNA methylation studies suggest that CRCs can be divided into at least three-four subtypes according to the frequency of DNA methylation and those of mutations in key CRC genes. Despite hundreds of genes might be epigenetically modified in CRC cells, there is interest in the identification of DNA methylation biomarkers to be used for CRC diagnosis, progression, tendency to tissue invasion and metastasis, prognosis, and response to chemotherapeutic agents. Moreover, DNA methylation largely depends on one-carbon metabolism, the metabolic pathway required for the production of S-adenosylmethionine, the major intracellular methylating agent. Complex interactions are emerging among dietary one-carbon nutrients (folates, vitamin B6, vitamin B12, methionine, and others), their metabolic genes, CRC risk, and DNA methylation profiles in CRC. Moreover, active research is also focused on the possible contribution of folic acid dietary fortification during pregnancy and the possible methylation of CRC-related genes in the offspring.
Cancer letters.Cancer Lett.2014 Jan 28;342(2):238-47. doi: 10.1016/j.canlet.2011.12.030. Epub 2011 Dec 24.
The original theory of the multi-step process of colorectal cancer (CRC), suggesting that the disease resulted from the accumulation of mutations in oncogenes and tumor suppressor genes in colonic mucosa cells, has been largely revised following the observation that epigenetic modifications of sever
PMID 22202641

Japanese Journal

Can an Inhibitor of DNA Polymerase β Enhance the Formation of Comet Tail?

Odajima Chihiro,Nakamura Takanori,Miura Masanori [他],YAMAZAKI Kayoko,HONDA Gisho,KIKUCHI Yasuaki,YAMAMOTO Ayumi,SASAKI Yu F.
Genes and environment : the official journal of the Japanese Environmental Mutagen Society 35(2), 46-52, 2013-05-20
… Aphidicolin (APC) and the combination of cytosine-1-β-D-arabinofuranoside and hydroxyurea (araC/HU) enhanced comet-tail formation by UV, a UV-mimetic agent, 4-nitroquinoline-1-oxide (4NQO), and methylating agents, methyl methanesulfonate (MMS) and methyl nitrosourea (MNU). …
NAID 10031158580

TMP塩基によるホウ素原子置換ベンゼンのオルトメタル化反応の開発

河内敦,長江沙織,尾野上康裕,山本陽介
基礎有機化学討論会要旨集（基礎有機化学連合討論会予稿集） 2008(0), 115-115, 2008
ホウ素原子置換ベンゼンのオルト位をメタル化するために，メタルへの配位可能な窒素原子部位を有するN-メチル-1,3-ジアミノプロパンをホウ素原子上に導入した1を合成した。1に，塩基として(TMP) 2MgをTHF中還流下で作用させることで，低 …
NAID 130004645220

遷移金属触媒と有機亜鉛または有機ホウ素を活用した高効率有機合成反応の開発

木村正成
有機合成化学協会誌 : JOURNAL OF Synthetic Organic Chemistry JAPAN 64(2), 130-140, 2006-02-01
… In place of diethylzinc, dimethylzinc serves as a methylating agent to evoke the three-component coupling reaction of methyl group, 1, 3-dienes, and carbonyls to provide 3-hexenols in excellent yields. …
NAID 10017252327