65475-51-6Relevant articles and documents
Independent Generation of Reactive Intermediates Leads to an Alternative Mechanism for Strand Damage Induced by Hole Transfer in Poly(dA-T) Sequences
Sun, Huabing,Zheng, Liwei,Greenberg, Marc M.
, p. 11308 - 11316 (2018/09/13)
Purine radical cations (dA?+ and dG?+) are the primary hole carriers of DNA hole migration due to their favorable oxidation potential. Much less is known about the reactivity of higher energy pyrimidine radical cations. The thymidine radical cation (T?+) was produced at a defined position in DNA from a photochemical precursor for the first time. T?+ initiates hole transfer to dGGG triplets in DNA. Hole localization in a dGGG sequence accounts for ～26% of T?+ formed under aerobic conditions in 9. Reduction to yield thymidine is also quantified. 5-Formyl-2′-deoxyuridine is formed in low yield in DNA when T?+ is independently generated. This is inconsistent with mechanistic proposals concerning product formation from electron transfer in poly(dA-T) sequences, following hole injection by a photoexcited anthraquinone. Additional evidence that is inconsistent with the original mechanism was obtained using hole injection by a photoexcited anthraquinone in DNA. Instead of requiring the intermediacy of T?+, the strand damage patterns observed in those studies, in which thymidine is oxidized, are reproduced by independent generation of 2′-deoxyadenosin-N6-yl radical (dA?). Tandem lesion formation by dA? provides the basis for an alternative mechanism for thymidine oxidation ascribed to hole migration in poly(dA-T) sequences. Overall, these experiments indicate that the final products formed following DNA hole transfer in poly(dA-T) sequences do not result from deprotonation or hydration of T?+, but rather from deprotonation of the more stable dA?+, to form dA?, which produces tandem lesions in which 5′-flanking thymidines are oxidized.
Chemoenzymatic synthesis of 3′-O-acetal-protected 2′-deoxynucleosides as building blocks for nucleic acid chemistry
Rodriguez-Perez, Tatiana,Fernandez, Susana,Martinez-Montero, Saul,Gonzalez-Garcia, Tania,Sanghvi, Yogesh S.,Gotor, Vicente,Ferrero, Miguel
experimental part, p. 1736 - 1744 (2010/06/13)
We have developed a simple and convenient synthetic strategy for the preparation of tetrahydropyranyl, 4-methoxy-tetrahydropyranyl, and tetrahydrofuranyl ethers of 2′-deoxynucleosides, which are useful building blocks for nucleic acid chemistry. Enzymatic benzoylation provides an efficient alternative for protecting the 5′-hydroxy group of the parent nucleosides in a regioselective manner. Subsequently, tetrahydropyranylation and tetrahydrofuranylation of the 2′-deoxynucleosides at the 3′-hydroxy group were accomplished with p-toluensulfonic acid, MgBr2, or camphorsulfonic acid as catalysts. Deprotection of the 5′-O-benzoyl group furnished 3′-O-acetal-protected 2′-deoxynucleosides. The three-step process is expected to enable the large-scale synthesis of protected nucleosides.
Direct measurement of pyrimidine C6-hydrate stability
Nolan Carter,Greenberg, Marc M.
, p. 2341 - 2346 (2007/10/03)
Pyrimidine C6-hydrates are produced via UV-irradiation and undergo dehydration upon standing. The stability of these compounds has a direct bearing on their genotoxicity. The rate constants for elimination from 5' -benzyoylated derivatives of 5,6-dihydro- 5-hydroxythymidine (6) and 5,6-dihydro-5-hydroxy-2' -deoxyuridine (9) were measured directly via HPLC. The rate constants for dehydration increase from pH 6.0 to 8.0. The half-lives for 6 and 9 at pH 7.4 and 37°C are 46.5 and 24.4 h, respectively. Deglycosylation is not observed, even upon heating at 90°C. These observations reinforce proposals that pyrimidine hydrates are sufficiently long-lived that they can exert significant effects on biological systems. Copyright
