THE CHEMISTRY OF SINGLE-STRANDED 4'-DNA RADICALS - INFLUENCE OF THE RADICAL PRECURSOR ON ANAEROBIC AND AEROBIC STRAND CLEAVAGE

被引：93

作者：

GIESE, B

BEYRICHGRAF, X

ERDMANN, P

PETRETTA, M

SCHWITTER, U

机构：

[1] Department of Chemistry, University of Basel, CH-4056 Basel

来源：

CHEMISTRY & BIOLOGY | 1995年 / 2卷 / 06期

基金：

美国国家科学基金会;

关键词：

DNA CLEAVAGE; DNA HYDROPEROXIDES; 4'-DNA RADICAL; MODIFIED OLIGONUCLEOTIDES;

D O I：

10.1016/1074-5521(95)90217-1

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Background: Deoxyribosylnucleotide radicals with a radical center at the 4'-position are important intermediates in radical-induced DNA strand cleavage. In the presence of O-2, these DNA radicals yield cleavage products that are partly oxidized. In the past, the postulated peroxide intermediates could not be detected directly because they were unstable under the conditions of either radical generation, the work-up procedure, or the analytical techniques used. We set out to generate and analyze these crucial intermediates in radical-induced DNA strand cleavage under mild conditions. Results: Photolysis experiments with modified single-stranded oligonucleotides generated 4'-DNA radicals that were trapped by O-2. Using MALDT-MS, DNA peroxides could be detected directly. Depending upon the precursor, these peroxides are formed either before or after the cleavage of the single-stranded DNA radical. Reactions in the presence of O-18(2) and/or (H2O)-O-18 as well as subsequent transformations to the oxidized cleavage products confirmed the structure of the DNA peroxides. Conclusions: Our technique of selective DNA radical generation under mild conditions makes it possible to detect labile reaction products of single-stranded DNA radicals and to gain further insight into their cleavage reactions. In cases where a radical pair is formed, the shielding effect protects the DNA radical from external attack so that cleavage of the single strand competes successfully with trapping by O-2. This shielding effect might be of general importance if the DNA radicals are generated by reagents that bind to the DNA.

引用

页码：367 / 375

页数：9

共 17 条

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