DNA cleavage specificity of a group of cationic metalloporphyrins.
DNA cleavage specificity of a group of cationic metalloporphyrins.
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DOI：
10.1021/bi00370a021
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发表时间：
1986-11
期刊：
影响因子：
2.9
通讯作者：
B. Ward;A. Skorobogaty;J. Dabrowiak
中科院分区：
文献类型：
--
作者：
B. Ward;A. Skorobogaty;J. Dabrowiak
研究了一组水溶性金属卟啉对DNA的切割能力。在抗坏血酸、超氧离子或碘苯存在下，meso-tetrakis(N-methyl-4-pyridiniumyl)porphine的Mn3+、Fe3+或Co3+络合物(H_2T4MPyP)与DNA孵育会导致DNA断裂。将卟啉自毁速率与共价闭合环状PM2 DNA的断链速率进行比较，表明在切割过程中，卟啉保持不变。用凝胶electrophoresis/autoradiography/microdensitometry对pBR322DNA的139bp限制性片段上的卟啉介导的链断裂进行分析，发现最小的卟啉裂解位点是(A X T)3。在给定的位点内的切割模式是不对称的，这表明卟啉结合和链断裂过程具有很强的方向性。本文从甲基丙基铁-EDTA和铁博莱霉素的DNA断裂机理分析了卟啉介导的DNA断裂机理，并讨论了阳离子金属卟啉作为足迹探针和新的DNA“报告配体”的潜力。
The ability of a group of water-soluble metalloporphyrins to cleave DNA has been investigated. Incubation of Mn3+, Fe3+, or Co3+ complexes of meso-tetrakis(N-methyl-4-pyridiniumyl)porphine (H2T4MPyP) with DNA in the presence of ascorbate, superoxide ion, or iodosobenzene results in DNA breakage. Comparisons between the rates of porphyrin autodestruction with the rates of strand scission of covalently closed circular PM2 DNA indicate that the porphyrins remain intact during the cleavage process. Analysis of the porphyrin-mediated strand scissions on a 139-base-pair restriction fragment of pBR322 DNA using gel electrophoresis/autoradiography/microdensitometry reveals that the minimum porphyrin cleavage site is (A X T)3. The cleavage pattern within a given site was found to be asymmetric, indicating that porphyrin binding and the strand scission process are highly directional in nature. In addition to an analysis of the mechanism of porphyrin-mediated strand breakage in terms of the DNA cleavage mechanism of methidium-propyl-iron-EDTA and Fe-bleomycin, the potential of the cationic metalloporphyrins as footprinting probes and as new "reporter ligands" for DNA is presented and discussed.