A novel vicinal lesion obtained from the oxidative photosensitization of TpdG: Characterization and mechanistic aspects

被引:33
作者
Delatour, T
Douki, T
Gasparutto, D
Brochier, MC
Cadet, J
机构
[1] CEA, Dept Rech Fondamentale Mat Condensee, SCIB, LAN,Lab Les Acides Nucl, F-38054 Grenoble 9, France
[2] Univ Grenoble 1, LEDSS, F-38400 St Martin Dheres, France
关键词
D O I
10.1021/tx980066w
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A new type of vicinal base lesion was isolated from the photosensitization of TpdG in aerated aqueous solution. One- and two-dimensional NMR measurements were used together with mass spectrometry to accurately characterize the new adduct. Chemical detection of guanidine provided additional structural information on the base moiety at the 3'-OH terminal end. Altogether the experiments results were indicative of the occurrence of a covalent bonding between the pyrimidine ring on the 5'-OH terminal end and the imidazole ring on the 3'-OH terminal end through a methylene bridge. Photosensitization studies of TpdG, thymidine, and 2'-deoxyguanosine in the presence of either benzophenone, menadione, or riboflavin associated with isotopic labeling experiments using enriched oxygen and water provided relevant information on the mechanism of formation of the adduct. The results of these experiments clearly demonstrated that the initial event leading to the formation of the lesion is the abstraction of a hydrogen atom from the methyl group of the thymine base moiety of TpdG. This is followed by the addition of the methyl-centered radical to the C-4 atom of the guanine ring which gives rise to the vicinal lesion after reaction with molecular oxygen and subsequent rearrangement.
引用
收藏
页码:1005 / 1013
页数:9
相关论文
共 58 条
  • [1] CONFORMATIONAL-ANALYSIS OF SUGAR RING IN NUCLEOSIDES AND NUCLEOTIDES - NEW DESCRIPTION USING CONCEPT OF PSEUDOROTATION
    ALTONA, C
    SUNDARALINGAM, M
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1972, 94 (23) : 8205 - +
  • [2] CONFORMATIONAL-ANALYSIS OF SUGAR RING IN NUCLEOSIDES AND NUCLEOTIDES - IMPROVED METHOD FOR INTERPRETATION OF PROTON MAGNETIC-RESONANCE COUPLING-CONSTANTS
    ALTONA, C
    SUNDARALINGAM, M
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1973, 95 (07) : 2333 - 2344
  • [3] High-intensity UV laser photolysis of DNA and purine 2'-deoxyribonucleosides: Formation of 8-oxopurine damage and oligonucleotide strand cleavage as revealed by HPLC and gel electrophoresis studies
    Angelov, D
    Spassky, A
    Berger, M
    Cadet, J
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1997, 119 (47) : 11373 - 11380
  • [4] ANGELOV D, 1994, TRENDS PHOTOCHEM PHO, V3, P643
  • [5] A NOVEL INTRAMOLECULAR HYDROGEN-BOND IN THE CRYSTAL-STRUCTURE OF 5-HYDROXYMETHYL-2'-DEOXYURIDINE, AN ANTI-VIRAL AND ANTI-NEOPLASTIC NUCLEOSIDE - CONFORMATIONAL-ANALYSIS OF THE DEOXYRIBOSE RING
    BIRNBAUM, GI
    DESLAURIERS, R
    LIN, TS
    SHIAU, GT
    PRUSOFF, WH
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1980, 102 (12) : 4236 - 4241
  • [6] BOLLUM FJ, 1963, BIOCHIM BIOPHYS ACTA, V68, P599
  • [7] VICINAL LESIONS IN X-IRRADIATED DNA
    BOX, HC
    BUDZINSKI, EE
    FREUND, HG
    EVANS, MS
    PATRZYC, HB
    WALLACE, JC
    MACCUBBIN, AE
    [J]. INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 1993, 64 (03) : 261 - 263
  • [8] FREE RADICAL-INDUCED DOUBLE-BASE LESIONS
    BOX, HC
    FREUND, HG
    BUDZINSKI, EE
    WALLACE, JC
    MACCUBBIN, AE
    [J]. RADIATION RESEARCH, 1995, 141 (01) : 91 - 94
  • [9] Free radical-induced tandem base damage in DNA oligomers
    Box, HC
    Budzinski, EE
    Dawidzik, JB
    Gobey, JS
    Freund, HG
    [J]. FREE RADICAL BIOLOGY AND MEDICINE, 1997, 23 (07) : 1021 - 1030
  • [10] Radiation-induced formation of a crosslink between base moieties of deoxyguanosine and thymidine in deoxygenated solutions of d(CpGpTpA)
    Box, HC
    Budzinski, EE
    Dawidzik, JD
    Wallace, JC
    Evans, MS
    Gobey, JS
    [J]. RADIATION RESEARCH, 1996, 145 (05) : 641 - 643