63844-76-8Relevant articles and documents
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Pal
, p. 5170,5173 (1978)
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Products of the reaction between a diazoate derivative of 2′-deoxycytidine and L-Lysine and its implication for DNA - Nucleoprotein cross-linking by NO or HNO2
Suzuki, Toshinori,Yamada, Masaki,Nakamura, Takanori,Ide, Hiroshi,Kanaori, Kenji,Tajima, Kunihiko,Morii, Takashi,Makino, Keisuke
, p. 1223 - 1227 (2000)
Recently, we have reported that a stable diazoate intermediate (dCyd-diazoate) is produced upon the reaction of dCyd with nitrous acid and nitric oxide [Suzuki, T., Nakamura, T., Yamada, M., Ide, H., Kanaori, K., Tajima, K., Morii, T., and Makino, K. (1999) Biochemistry 38, 7151-7158]. In this work, the reaction of dCyd-diazoate with L-Lys was investigated. When 0.4 mM dCyd-diazoate was incubated with 10 mM L-Lys in sodium phosphate buffer (pH 7.4) at 37 °C, two unknown products were formed in addition to dUrd. By spectrometric measurements, the products were identified as dCyd-Lys adducts with C4(dCyd)-Nα(Lys) and C4(dCyd)-N∈(Lys) linkages (abbreviated as dCyd-αLys and dCyd-∈Lys, respectively). The yields at the reaction time of 72 h were 28.0% dCyd-αLys, 13.4% dCyd-∈Lys, and 11.1% dUrd with 33.9% unreacted dCyd-diazoate. When 0.4 mM dCyd-diazoate was incubated with 22 mg/mL poly(L-Lys) at pH 7.4 and 37 °C for 24 h, 82% of the free dCyd-diazoate disappeared, indicating adduct formation with the polymer. At pH 7.4 and 37 °C, dCyd-αLys and dCyd-∈Lys were fairly stable and gave rise to no product after incubation for 7 days. At pH 4.0 and 70 °C, both adducts disappeared with the same first-order rate constant of 1.7 x 10-6 s-1 (t1/2 = 110 h), which was ～1/3 of that of dCyd. These results suggest that if dCyd-diazoate is formed in DNA in vivo, it may react with free L-Lys and the side chain of L-Lys in nucleoproteins, resulting in stable adducts and DNA-protein cross-links, respectively.
Reactivity and DNA Damage by Independently Generated 2′-Deoxycytidin-N4-yl Radical
Peng, Haihui,Jie, Jialong,Mortimer, Ifor P.,Ma, Zehan,Su, Hongmei,Greenberg, Marc M.
, p. 14738 - 14747 (2021/09/18)
Oxidative stress produces a variety of radicals in DNA, including pyrimidine nucleobase radicals. The nitrogen-centered DNA radical 2′-deoxycytidin-N4-yl radical (dC·) plays a role in DNA damage mediated by one electron oxidants, such as HOCl and ionizing radiation. However, the reactivity of dC· is not well understood. To reduce this knowledge gap, we photochemically generated dC· from a nitrophenyl oxime nucleoside and within chemically synthesized oligonucleotides from the same precursor. dC· formation is confirmed by transient UV-absorption spectroscopy in laser flash photolysis (LFP) experiments. LFP and duplex DNA cleavage experiments indicate that dC· oxidizes dG. Transient formation of the dG radical cation (dG+?) is observed in LFP experiments. Oxidation of the opposing dG in DNA results in hole transfer when the opposing dG is part of a dGGG sequence. The sequence dependence is attributed to a competition between rapid proton transfer from dG+?to the opposing dC anion formed and hole transfer. Enhanced hole transfer when less acidicO6-methyl-2′-deoxyguanosine is opposite dC· supports this proposal. dC· produces tandem lesions in sequences containing thymidine at the 5′-position by abstracting a hydrogen atom from the thymine methyl group. The corresponding thymidine peroxyl radical completes tandem lesion formation by reacting with the 5′-adjacent nucleotide. As dC· is reduced to dC, its role in the process is traceless and is only detectable because of the ability to independently generate it from a stable precursor. These experiments reveal that dC· oxidizes neighboring nucleotides, resulting in deleterious tandem lesions and hole transfer in appropriate sequences.
Novel Use
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Paragraph 0020, (2019/05/24)
The invention relates to the use of an amine masked moiety in a method of enzymatic nucleic acid synthesis. The invention also relates to said amine masked moieties per se and a process for preparing nucleotide triphosphates comprising said amine masked moieties.
