Dynamics of bleomycin interaction with a strongly bound hairpin DNA substrate, and implications for cleavage of the bound DNA.

Dynamics of bleomycin interaction with a strongly bound hairpin DNA substrate, and implications for cleavage of the bound DNA.
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DOI:
10.1021/ja306233e
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发表时间:
2012-10-31
影响因子:
15
通讯作者:
Hecht SM
Hecht SM
中科院分区:
化学1区
文献类型:
--
作者:
Bozeman TC;Nanjunda R;Tang C;Liu Y;Segerman ZJ;Zaleski PA;Wilson WD;Hecht SM

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最近的研究表明,与博来霉素强烈结合的DNAs被抗肿瘤抗生素降解,其特征不同于在过量Fe·BLM存在下研究随机选择的DNA的切割时观察到的特征。在本研究中,表面等离子体共振已被用来表征BLM B2结合到一个强结合的发夹DNA的动力学,以确定Fe 3+,盐和温度对BLM-DNA相互作用的影响。一个强大的主要DNA结合位点,至少有一个弱得多的网站被记录。相比之下,发现了一个以上的强切割位点,还对另外两个发夹DNA进行了观察。证据是BLM平衡之间的较强和较弱的结合位点的方式,使BLM不可用的其他,较强的绑定DNA。因此,与给定位点的结合增强并不一定导致该位点的DNA降解增加,即对于强结合的DNA,DNA切割的便利性必须涉及除了从DNA糖中提取C-4′ H原子的固有速率之外的参数。
Recent studies involving DNAs bound strongly by bleomycins have documented that such DNAs are degraded by the antitumor antibiotic with characteristics different from those observed when studying the cleavage of randomly chosen DNAs in the presence of excess Fe•BLM. In the present study, surface plasmon resonance has been used to characterize the dynamics of BLM B2 binding to a strongly bound hairpin DNA, to define the effects of Fe3+, salt and temperature on BLM–DNA interaction. One strong primary DNA binding site, and at least one much weaker site was documented. In contrast, more than one strong cleavage site was found, an observation also made for two other hairpin DNAs. Evidence is presented for BLM equilibration between the stronger and weaker binding sites in a way that renders BLM unavailable to other, less strongly bound DNAs. Thus enhanced binding to a given site does not necessarily result in increased DNA degradation at that site, i.e. for strongly bound DNAs, the facility of DNA cleavage must involve parameters in addition to the intrinsic rate of C-4′ H atom abstraction from DNA sugars.
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