Mechanism of bleomycin: evidence for a rate-determining 4'-hydrogen abstraction from poly(dA-dU) associated with the formation of both free base and base propenal.
Mechanism of bleomycin: evidence for a rate-determining 4'-hydrogen abstraction from poly(dA-dU) associated with the formation of both free base and base propenal.
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博来霉素的作用机制：从与游离碱和碱丙烯醛的形成相关的聚（dA-dU）中决定速率的 4-氢提取的证据。
DOI：
10.1021/bi00347a009
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发表时间：
1985
期刊：
影响因子：
2.9
通讯作者：
Stubbe,J
中科院分区：
文献类型：
--
作者：
Wu,JC;Kozarich,JW;Stubbe,J
Department of Biochemistry，College of Agriculture and Life Sciences，University of威斯康星州，麦迪逊，威斯康星州53706接收1985年5月16日摘要：当poly（dA-[4/-3 H] dU）在各种条件下被活化的博莱霉素降解时，50 ~ 10%的脱氧尿苷残基转化为尿嘧啶和尿嘧啶丙烯醛，与DNA的观察结果平行.通过控制溶液中O2的浓度，尿嘧啶丙烯醛与尿嘧啶的相对比例可以在0。03用于厌氧活化，7.0用于在3atm的O2下活化。在这些条件下还测量了氚对4 '-氢提取的选择效应，发现其范围为7.2 - 12.5。这些结果强烈表明，尿嘧啶和尿嘧啶丙烯醛的形成是速率决定性的4 '-碳-氢键断裂和由该断裂产生的中间体的O2依赖性分配的结果。博来霉素是一类糖肽衍生的抗生素，具有良好的降解DNA的能力。该反应需要金属离子，如Fe（II）或Cu（I），和O2，并产生作为单体产物的游离核酸碱基和碱基丙烯1 *（图1）（Kuramochi等人，1981; Burger等人，1980，1981; Sausville等人，1976; Oppenheimer等人，1981; Rodriguez和Hecht，1982; Giloni等人，1981年; Eschlafeld等人，1985年）。此外，Burger et al.（1982）已经证明，Fe（III）和H2 O2在厌氧条件下也可以活化博来霉素，并且在与DNA相互作用时仅产生游离碱。已经提出碱丙烯醛的形成是由活化的博来霉素从脱氧核糖部分的C-4 '位上自由基夺取氢，然后形成不稳定的4'-氢过氧化物引起的（Giloni等人，1981年）。氢过氧化物被认为是分解，以提供DNA链断裂和碱丙烯醛。Burger等人的后续重要研究。（1982）提出，碱基丙烯醛的形成与DNA断裂是化学计量的，并且需要额外的O2。游离碱释放似乎不需要额外的O2超过博莱霉素活化所需的，并与碱不稳定位点的形成化学计量。
Department of Biochemistry, College of Agriculture and Life Sciences, University of Wisconsin, Madison, Wisconsin 53706 Received May 16, 1985 abstract: When poly (dA-[4/-3H] dU) was degraded by activated bleomycin under a variety of conditions, 50 ą 10% of the deoxyuridine residues were converted to uracil and uracil propenal, paralleling observations made with DNA. By manipulation of the concentration of 02 in solution, the relative ratio of uracilpropenal to uracil could be varied between0. 03 for anaerobic activation and 7.0 for activationat 3 atm of 02. Tritium selection effects on 4'-hydrogen abstraction were also measuredunder these conditions and found to range from 7.2 to 12.5. These results strongly suggest that the formation of both uracil and uracil propenal is the consequence of a rate-determining 4'-carbon-hydrogen bondcleavage and of an 02-dependent partitioning of the intermediate produced by this cleavage. e bleomycins, a glycopeptide-derived class of antibiotics, have a well-established ability to degrade DNA. The reaction requires metal ions, such as Fe (II) or Cu (I), and Oz and yields, as monomeric products, free nucleic acid bases and base propenals1*(Figure 1)(Kuramochi et al., 1981; Burger et al., 1980, 1981; Sausville et al., 1976; Oppenheimer et al., 1981; Rodriguez & Hecht, 1982; Giloni et al., 1981; Ehrenfeld et al., 1985). In addition, Burger et al.(1982) have demonstrated that Fe (III) and H202 under anaerobic conditions can also activate bleomycin and yield, upon interaction with DNA, exclusively free base. Base propenal formation has been proposed to resultfrom a radical abstraction of the hydrogen from the C-4'position of the deoxyribose moiety by the ac-tivated bleomycin followed by formation of an unstable 4'-hydroperoxide (Giloni et al., 1981). The hydroperoxide was proposed to decompose to afford DNA strand scission and the base propenal. Subsequent important studies by Burger et al.(1982) suggested that base propenal formation was stoichiometric with DNA scission and required additional 02. Free base release appearedto require no additional 02 beyond that required for bleomycin activation and was stoichiometric with the formation of alkaline-labile sites.
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亚铁离子和氧在博来霉素降解 DNA 中的作用。
DOI：
10.1016/0006-291x(76)90882-2
发表时间：
1976
影响因子：
3.1
作者：
E. Sausville;J. Peisach;S. Horwitz
通讯作者：
S. Horwitz
博来霉素 DNA 链断裂和醛形成的化学计量。
DOI：
--
发表时间：
1982
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Burger,RM;Peisach,J;Horwitz,SB
通讯作者：
Horwitz,SB
DOI：
--
发表时间：
1981
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Oppenheimer,NJ;Chang,C;Rodriguez,LO;Hecht,SM
通讯作者：
Hecht,SM
大肠杆菌核糖核苷二磷酸还原酶的作用机制。
影响因子：
4.8
作者：
JoAnne Stubbe;M. Ator;T. Krenitsky
通讯作者：
T. Krenitsky
DOI：
10.1016/s0021-9258(19)70209-9
发表时间：
1980-12
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
R. Burger;Allen R. Berkowitz;J. Peisach;Susan Band
通讯作者：
R. Burger;Allen R. Berkowitz;J. Peisach;Susan Band