- Deamination, oxidation, and C-C bond cleavage reactivity of 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxycytosine
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Three new cytosine derived DNA modifications, 5-hydroxymethyl-2′- deoxycytidine (hmdC), 5-formyl-2′-deoxycytidine (fdC) and 5-carboxy-2′-deoxycytidine (cadC) were recently discovered in mammalian DNA, particularly in stem cell DNA. Their function is currently not clear, but it is assumed that in stem cells they might be intermediates of an active demethylation process. This process may involve base excision repair, C-C bond cleaving reactions or deamination of hmdC to 5-hydroxymethyl-2′- deoxyuridine (hmdU). Here we report chemical studies that enlighten the chemical reactivity of the new cytosine nucleobases. We investigated their sensitivity toward oxidation and deamination and we studied the C-C bond cleaving reactivity of hmdC, fdC, and cadC in the absence and presence of thiols as biologically relevant (organo)catalysts. We show that hmdC is in comparison to mdC rapidly oxidized to fdC already in the presence of air. In contrast, deamination reactions were found to occur only to a minor extent. The C-C bond cleavage reactions require the presence of high concentration of thiols and are acid catalyzed. While hmdC dehydroxymethylates very slowly, fdC and especially cadC react considerably faster to dC. Thiols are active site residues in many DNA modifiying enzymes indicating that such enzymes could play a role in an alternative active DNA demethylation mechanism via deformylation of fdC or decarboxylation of cadC. Quantum-chemical calculations support the catalytic influence of a thiol on the C-C bond cleavage.
- Schiesser, Stefan,Pfaffeneder, Toni,Sadeghian, Keyarash,Hackner, Benjamin,Steigenberger, Barbara,Schroeder, Arne S.,Steinbacher, Jessica,Kashiwazaki, Gengo,Hoefner, Georg,Wanner, Klaus T.,Ochsenfeld, Christian,Carell, Thomas
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supporting information
p. 14593 - 14599
(2013/10/22)
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- Synthesis, structure and imaging of oligodeoxyribonucleotides with tellurium-nucleobase derivatization
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We report here the first synthesis of 5-phenyl-telluride-thymidine derivatives and the Te-phosphoramidite. We also report here the synthesis, structure and STM current-imaging studies of DNA oligonucleotides containing the nucleobases (thymine) derivatize
- Sheng, Jia,Hassan, Abdalla E. A.,Zhang, Wen,Zhou, Jianfeng,Xu, Bingqian,Soares, Alexei S.,Huang, Zhen
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p. 3962 - 3971
(2012/03/26)
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- NOVEL COMPOUNDS AND DERIVATIZATION OF DNAS AND RNAS ON THE NUCLEOBASES OF PYRIMIDINES FOR FUNCTION, STRUCTURE, AND THERAPEUTICS
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Disclosed are compounds of formula (I)3 a derivative, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer. Also disclosed are methods of preparing compound of formula (I), a derivative, or a tautomer thereof, or
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Page/Page column 50
(2010/12/18)
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- Protecting groups transfer: Unusual method of removal of tr and TBDMS groups by transetherification
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The triphenylmethyl (Tr) group undergoes a transfer (transetherification or disproportionation) between the molecules of 5'-O-Tr-2'-deoxynucleosides in a process mediated by anhydrous sulfates of Cu+2, Fe+2, or Ni+2 to yield mixtures of 3',5'-bis-O-Tr and 3'-O-Tr products. If phenylmethanol is present in a reaction medium, detritylation results with concomitant formation of phenylmethyl triphenylmethyl ether. The behavior of t-butyldimethylsilyl (TBDMS) group in 5'-O-TBDMS-2'-deoxynucleosides is exactly the same. Such type of transetherifications was not observed before for the O-Tr and O-TBDMS groups. Copyright Taylor & Francis Group, LLC.
- Cabral, Nadia L. D.,Thiessen, Luciano Hoeltgebaum,Doboszewski, Bogdan
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p. 931 - 948
(2008/12/21)
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