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INTERACTIONS BETWEEN NUCLEIC ACIDS AND METALLOPORPHYRINS

核酸和金属卟啉之间的相互作用

基本信息

批准号：
08672478
负责人：
UNO Tadayuki
金额：
$ 1.41万
依托单位：
KUMAMOTO UNIVERSITY (1997-1998)The University of Tokushima (1996)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

项目摘要

The purpose of this research is to synthesize metalloporphyrins which can recognize a specific nucleotide sequence of nucleic acids and cleave them at a specific position, and to reveal the cleaving activity and interaction mechanism between them. First, I studied the interactions between nucleic acids and a water-soluble cationic porphyrin, tetramethylpyridylporphyrin (TMPyP). I employed synthetic DNA, RNA, and DNA RNA hybrids, and found that (1) TMPyP self-stacks in a minor groove of RNA duplexes, (2) TMPyP intercalates between the base-pairs of hybrid duplexes, and (3) TMPyP either binds to a minor groove electrostatically, or intercalates, depending on the sequence of DNA duplexes. I further studied the way to regulate the binding mode to DNA with the use of triplex formation. It was found that self-stacking and intercalation of the TMPyP were inhibited by the triplex formation, but the groove binding was promoted in that the number of binding sites of the TMPyP increased two-fold. The DNA cleaving activity of iron porphyrin and metal-free porphyrins was studied. The oxidative cleavage by peroxo-compounds was investigated in detail, and addition of imidazoles, which could be axial ligands of the iron, was found to promote the cleaving activity. A porphyrin periphery was introduced to give capability to recognize DNA sequences. In the porphyrin derivative having DNA-intercalating acridirie moiety, CD spectroscopy suggested that the porphyrin located in the minor groove of the DNA.The acridine-free TMPyP self-stacked on the DNA, and the binding mode was distinct that the binding was found to be achieved by the acridine intercalator.

本研究的目的是合成能够识别核酸特定核苷酸序列并在特定位置切割核酸的金属卟啉，并揭示它们之间的切割活性和相互作用机制。首先，我研究了核酸和水溶性阳离子卟啉，四甲基吡啶卟啉（TMPyP）之间的相互作用。我使用了合成的DNA、RNA和DNA RNA杂交体，发现（1）TMPyP在RNA双链体的小沟中自我堆叠，（2）TMPyP插入杂交双链体的碱基对之间，（3）TMPyP要么静电结合小沟，要么插入，这取决于DNA双链体的序列。我进一步研究了如何利用三链体形成来调节与DNA的结合模式。结果发现，自堆积和嵌入的TMPyP的抑制由三链体的形成，但槽结合的促进，TMPyP的结合位点的数量增加了两倍。研究了铁卟啉和无金属卟啉的DNA切割活性。详细研究了过氧化合物的氧化裂解，发现添加咪唑类化合物（可能是铁的轴向配体）可促进裂解活性。引入卟啉外围以提供识别DNA序列的能力。CD光谱表明，在含有DNA嵌入剂吖啶的卟啉衍生物中，卟啉位于DNA的小沟中，不含吖啶的TMPyP在DNA上自堆积，结合方式明显，是通过吖啶嵌入剂实现的。