- Intramolecular Stacking Association of Three Dinucleoside Monophosphates Containing Naturally-occurring 1-Methyladenosine Residue(s): m1ApA. Apm1A, m1Apm1A
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Three modified dinucleoside monophosphates containing naturally-occurring 1-methyladenosine residue, m1ApA, Apm1A, and m1Apm1A, were prepared.Intramolecular stacking association properties of these dimers were studied quantitatively using two independent methods.Thermal denaturation and acid-base titration experiments reached to the same conclusion that both m1pA and Apm1 were less stacked than ApA.Acid-base titration experiment also showed that the three modified dimers, in their neutral forms, were stacked to almost the same extent as ApA.These results indicate the N-1 methylation of an adenine base does not enhance stacking interaction of dimers, in sharp contrast to the N6 methylation of the same base.UV hypochromicity and CD measurements were also made for the three dimers, and the results were found to be consistent with those of th estacking quotient determination.
- Takeuchi, Yasuhiro,Tazawa, Ichiro,Inoue, Yasuo
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- Identification of Flavin Mononucleotide as a Cell-Active Artificial N6-Methyladenosine RNA Demethylase
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N6-Methyladenosine (m6A) represents a common and highly dynamic modification in eukaryotic RNA that affects various cellular pathways. Natural dioxygenases such as FTO and ALKBH5 are enzymes that demethylate m6A residues in mRNA. Herein, the first identification of a small-molecule modulator that functions as an artificial m6A demethylase is reported. Flavin mononucleotide (FMN), the metabolite produced by riboflavin kinase, mediates substantial photochemical demethylation of m6A residues of RNA in live cells. This study provides a new perspective to the understanding of demethylation of m6A residues in mRNA and sheds light on the development of powerful small molecules as RNA demethylases and new probes for use in RNA biology.
- Xie, Li-Jun,Yang, Xiao-Ti,Wang, Rui-Li,Cheng, Hou-Ping,Li, Zhi-Yan,Liu, Li,Mao, Lanqun,Wang, Ming,Cheng, Liang
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supporting information
p. 5028 - 5032
(2019/03/17)
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- Noncanonical RNA Nucleosides as Molecular Fossils of an Early Earth—Generation by Prebiotic Methylations and Carbamoylations
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The RNA-world hypothesis assumes that life on Earth started with small RNA molecules that catalyzed their own formation. Vital to this hypothesis is the need for prebiotic routes towards RNA. Contemporary RNA, however, is not only constructed from the four canonical nucleobases (A, C, G, and U), it also contains many chemically modified (noncanonical) bases. A still open question is whether these noncanonical bases were formed in parallel to the canonical bases (chemical origin) or later, when life demanded higher functional diversity (biological origin). Here we show that isocyanates in combination with sodium nitrite establish methylating and carbamoylating reactivity compatible with early Earth conditions. These reactions lead to the formation of methylated and amino acid modified nucleosides that are still extant. Our data provide a plausible scenario for the chemical origin of certain noncanonical bases, which suggests that they are fossils of an early Earth.
- Schneider, Christina,Becker, Sidney,Okamura, Hidenori,Crisp, Antony,Amatov, Tynchtyk,Stadlmeier, Michael,Carell, Thomas
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supporting information
p. 5943 - 5946
(2018/04/30)
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- New tools in nucleoside toolbox of tick-borne encephalitis virus reproduction inhibitors
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Design and development of nucleoside analogs is an established strategy in the antiviral drug discovery field. Nevertheless, for many viruses the coverage of structure-activity relationships (SAR) in the nucleoside chemical space is not sufficient. Here we present the nucleoside SAR exploration for tick-borne encephalitis virus (TBEV), a member of Flavivirus genus. Promising antiviral activity may be achieved by introduction of large hydrophobic substituents in the position 6 of adenosine or bulky silyl groups to the position 5′. Introduction of methyls to the ribose moiety does not lead to inhibition of TBEV reproduction. Possible mechanisms of action of these nucleosides include the inhibition of viral entry or interaction with TBEV non-structural protein 5 methyltransferase or RNA-dependent RNA polymerase domains.
- Orlov, Alexey A.,Drenichev, Mikhail S.,Oslovsky, Vladimir E.,Kurochkin, Nikolay N.,Solyev, Pavel N.,Kozlovskaya, Liubov I.,Palyulin, Vladimir A.,Karganova, Galina G.,Mikhailov, Sergey N.,Osolodkin, Dmitry I.
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supporting information
p. 1267 - 1273
(2017/06/19)
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- Methylation of Adenosine and Related Nucleosides with Trimethylselenonium Hydroxyde, and Regiospecific Effects of Copper(II) Ions
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Methylation of adenosine, deoxyadenosine, 6-N-methyladenosine and 2'(3')-O-methyladenosines with trimethylselenonium hydroxyde was studied in the presence and absence of copper(II) acetylacetonate .It was found that copper(II) ions promoted methylation of the 2'(3')-OH groups of the ribonucleosides but suppressed methylation at the N-1 position of the adenine rings.The metal-ion effects are discussed in conjunction with a catalytic role for Cu(AA)2 in the reactions.
- Yamauchi, Kiyoshi,Hattori, Kazue,Kinoshita, Masayoshi
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p. 1327 - 1330
(2007/10/02)
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- Methylation study of ribonucleosides, deoxyribonucleosides, and 2′-O-methylribonucleosides with trimethylsulphonium hydroxide and trimethylsulphonium iodide. Influence of the 2′-hydroxy-groups on the reactivity of the base moieties of ribonucleosides
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Methylations of the naturally occuring ribonucleoside (1), deoxyribonucleoside (2), and 2′-O-methylribonucleoside (3) were carried out using trimethylsulphonium hydroxide (Me3SOH) and trimethylsulphonium iodide (Me3Sl). The base moiety of (2) and (3) are more reactive than the corresponding base moiety of (1). The sites and extent of methylation of (2) are considerably different from those of (1), but are almost identical with those of (3). The reactivities of (1)-(3) are discussed in connection to an intramolecular interaction of the 2′-OH groups with the base moiety of (1). The methylating characteristics of Me 3SOH and Me3Sl are also described. The kinetics indicate an SN2 mechanism for methylation of nucleosides by Me 3S+ ions.
- Yamauchi, Kiyoshi,Nakagima, Toru,Kinoshita, Masayoshi
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p. 2787 - 2792
(2007/10/02)
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