Toward Efficient Zn(II)-Based Artificial Nucleases
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- 作者：Elisa Boseggia ; Maddalena Gatos ; Lorena Lucatello ; Fabrizio Mancin ; Stefano Moro ; Manlio Palumbo ; Claudia Sissi ; Paolo Tecilla ; Umberto Tonellato ; and Giuseppe Zagotto
- 刊名：Journal of the American Chemical Society
- 出版年：2004
- 出版时间：April 14, 2004
- 年：2004
- 卷：126
- 期：14
- 页码：4543 - 4549
- 全文大小：161K
- 年卷期：v.126,no.14(April 14, 2004)
- ISSN：1520-5126
文摘
A series of cis-cis-triaminocyclohexane Zn(II) complex-anthraquinone intercalator conjugates,designed in such a way to allow their easy synthesis and modification, have been investigated as hydrolyticcleaving agents for plasmid DNA. The ligand structure comprises a triaminocyclohexane platform linkedby means of alkyl spacers of different length (from C4 to C8) to the anthraquinone group which may intercalatethe DNA. At a concentration of 5 
M, the complex of the derivative with a C8 alkyl spacer induces thehydrolytic stand scission of supercoiled DNA with a rate of 4.6 × 10-6 s-1 at pH 7 and 37 
C. The conjugationof the metal complex with the anthraquinone group leads to a 15-fold increase of the cleavage efficiencywhen compared with the anthraquinone lacking Zn-triaminocyclohexane complex. The straightforwardsynthetic procedure employed, allowing a systematic change of the spacer length, made possible to gainmore insight on the role of the intercalating group in determining the reactivity of the systems. Comparisonof the reactivity of the different complexes shows a remarkable increase of the DNA cleaving efficiencywith the length of the spacer. In the case of too-short spacers, the advantages due to the increased DNAaffinity are canceled due to the incorrect positioning of the reactive group, thus leading to cleavage inhibition.
M, the complex of the derivative with a C8 alkyl spacer induces thehydrolytic stand scission of supercoiled DNA with a rate of 4.6 × 10-6 s-1 at pH 7 and 37 C. The conjugationof the metal complex with the anthraquinone group leads to a 15-fold increase of the cleavage efficiencywhen compared with the anthraquinone lacking Zn-triaminocyclohexane complex. The straightforwardsynthetic procedure employed, allowing a systematic change of the spacer length, made possible to gainmore insight on the role of the intercalating group in determining the reactivity of the systems. Comparisonof the reactivity of the different complexes shows a remarkable increase of the DNA cleaving efficiencywith the length of the spacer. In the case of too-short spacers, the advantages due to the increased DNAaffinity are canceled due to the incorrect positioning of the reactive group, thus leading to cleavage inhibition.