Solution properties and photonuclease activity of cationic bis-porphyrins linked with a series of aliphatic diamines
Solution properties and photonuclease activity of cationic bis-porphyrins linked with a series of aliphatic diamines
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DOI：
10.1248/cpb.49.1531
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发表时间：
2001-12-01
影响因子：
1.7
通讯作者：
Uno, T
中科院分区：
文献类型：
--
作者：
Yamakawa, N;Ishikawa, Y;Uno, T
有效的光诱导DNA切割剂的开发对于诸如癌症光动力疗法（PDT）的生物医学应用特别感兴趣。为此，我们合成了一系列具有不同长度二氨基烷基链的阳离子双卟啉化合物，N，N '-双{4-[10，15，20-三（1-甲基吡啶-4-基）卟啉-5-基]苯甲酰基}低聚亚甲基二胺六碘化物。预期它们显示出比单色团meso-四（4-N-甲基吡啶鎓基）卟啉（TMPyP）更有效的DNA光切割，已知TMPyP在光照下有效切割DNA。发现阳离子双卟啉在水溶液中自聚集，并通过形成分子间二聚体来解释聚集特性。由于保守型的圆二色谱的双卟啉诱导的Soret区域结合小牛胸腺DNA，我们分配他们的结合模式外自堆积的DNA表面上。它们使用质粒DNA的光核酸酶活性随着它们的接头烃的数量增加而降低，并且与它们的二聚化趋势很好地相关。叠氮阴离子N-3（-）的抑制作用和D_2O的增强作用表明，单线态氧可能参与了DNA的光裂解。
The development of efficient photo-induced DNA cleavage agents has been of particular interest for biomedical applications such as cancer photodynamic therapy (PDT). Toward this objective, we synthesized a series of cationic bis-porphyrins with various lengths of diamino alkyl linkage, N,N'-bis{4-[10,15,20-tris(1-methylpyridinium-4-yl)porphyrin-5-yl]benzoyl} oligomethylenediamine hexaiodide. They were expected to show more efficient photocleavage of DNA than unichromophore meso-tetrakis(4-N-methylpyridiniumyl)porphine (TMPyP), which is well known to cleave DNA effectively on illumination. The cationic bis-porphyrins were found to self-aggregate in aqueous solution, and the aggregation property was accounted for by the formation of an intermolecular dimer. Because conservative-type circular dichroism spectra of the bis-porphyrins were induced in the Soret region on binding to calf thymus DNA, we assigned their binding mode to outside self-stacking on the DNA surface. Their photonuclease activity using plasmid DNA decreased as the number of their linker hydrocarbons increased, and was well correlated with their tendency for dimerization. The inhibitory effect of azide anion, N-3(-), and the enhancement effect of D2O suggest that singlet oxygen was probably involved in the photocleavage of DNA.