Catalytic release of deoxyribonucleic acid bases by oxidation and reduction of an iron.bleomycin complex.

Catalytic release of deoxyribonucleic acid bases by oxidation and reduction of an iron.bleomycin complex.
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通过铁博莱霉素复合物的氧化和还原催化释放脱氧核糖核酸碱。

DOI:
10.1021/bi00585a023
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发表时间:
1979
期刊:
影响因子:
2.9
通讯作者:
L. Povirk
L. Povirk
中科院分区:
生物学3区
文献类型:
--
作者:
L. Povirk

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Lawrence F. Povirk摘要:博莱霉素,铁,DNA,氧,巯基的几个反应的动力学和化学计量学进行了检查,以评估其可能的作用,在降解DNA的博莱霉素。在博来霉素存在下Fe(II)的氧化产生铁(III)-博来霉素络合物,其具有在320-400 nm处具有宽肩的光学吸收光谱,其稳定数小时。如果在加入博来霉素之前允许Fe(II)氧化,则不会形成络合物。复合物被二硫苏糖醇还原速度比未螯合的Fe(III)快5倍,复合物的还原被高浓度的DNA抑制。然而,停流研究表明,当存在足够的DNA来结合大部分的铁(II)-博莱霉素时,其被分子氧氧化的速率比未结合的铁(II)-博莱霉素快60倍。在相同条件下,每摩尔DNA结合的铁(II)-IR的氧化。最近关于博来霉素降解DNA的研究(Sausville等人,1978 a,B)强烈地表明反应中的关键步骤是Fe(II)离子的氧化,该Fe(II)离子被结合到DNA的博来霉素分子螯合。大多数反应的最终产物已经被鉴定(Haidle等人,1972; Sausville等人,1978 b; Takeshita等人,1978),但Fe(II)氧化前后事件的精确顺序仍然是推测性的。由于Fe(II)(后藤等人,1970)和铁(II)-博来霉素(Sausville等,1976)在中性pH下快速氧化,即使在没有DNA的情况下,铁及其与博来霉素和DNA的复合物的氧化和还原动力学必须是
Lawrence F. Povirk abstract: The kinetics and stoichiometryof several reactions involving bleomycin, iron, DNA, oxygen, and sulfhydryls were examined in order to assess their possible role in degradation of DNA by bleomycin. Oxidation of Fe (II) in the presence of bleomycin resulted in an iron (III)-bleomycin complex, having an optical absorption spectrum with a broad shoulder at 320-400 nm, which was stable for several hours. If Fe (II) was allowed to oxidize before bleomycin addition, the complex did not form. The complex was reduced by dithiothreitol 5 times faster than unchelated Fe (III), and reduction of the complex was inhibited by high concentrations of DNA. However, stopped-flow studiesshowed that, when sufficient DNA was present to bind most of the iron (II)-bleomycin, its rate of oxidation by molecular oxygen was 60 times faster than that of unbound iron (II)-bleomycin. Under the same con-ditions, oxidation of each mole of DNA-bound iron (II)-lR. ecent studies of the degradation of DNA by bleomycin (Sausville et al., 1978a, b) strongly suggest that a critical step in the reaction is the oxidation of an Fe (II) ion which is chelated by a bleomycin molecule bound to DNA. Most of the final products of the reaction havebeen identified (Haidle et al., 1972; Sausville et al., 1978b; Takeshita et al., 1978), but theprecise sequence of events proceding and following Fe (II) oxidation remains speculative. Since both Fe (II)(Goto et al., 1970) and iron (II)-bleomycin (Sausville et al., 1976) oxidize rapidly at neutral pH, even in the absence of DNA, the kinetics of oxidation and reduction of iron and its complexes with bleomycin and DNA must be
DOI: --
发表时间: 1966-06
期刊: Genetics
影响因子: 3.3
作者:
P. Howard-Flanders;L. Theriot
通讯作者: P. Howard-Flanders;L. Theriot