Boseggia Elisa, Gatos Maddalena, Lucatello Lorena, Mancin Fabrizio, Moro Stefano, Palumbo Manlio, Sissi Claudia, Tecilla Paolo, Tonellato Umberto, Zagotto Giuseppe
Dipartimento di Scienze Chimiche e Istituto CNR Tecnologia delle Membrane-Sezione di Padova, Università di Padova, via Marzolo 1, I-35131 Padua, Italy.
J Am Chem Soc. 2004 Apr 14;126(14):4543-9. doi: 10.1021/ja039465q.
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 hydrolytic cleaving agents for plasmid DNA. The ligand structure comprises a triaminocyclohexane platform linked by means of alkyl spacers of different length (from C(4) to C(8)) to the anthraquinone group which may intercalate the DNA. At a concentration of 5 microM, the complex of the derivative with a C(8) alkyl spacer induces the hydrolytic stand scission of supercoiled DNA with a rate of 4.6 x 10(-6) s(-1) at pH 7 and 37 degrees C. The conjugation of the metal complex with the anthraquinone group leads to a 15-fold increase of the cleavage efficiency when compared with the anthraquinone lacking Zn-triaminocyclohexane complex. The straightforward synthetic procedure employed, allowing a systematic change of the spacer length, made possible to gain more insight on the role of the intercalating group in determining the reactivity of the systems. Comparison of the reactivity of the different complexes shows a remarkable increase of the DNA cleaving efficiency with the length of the spacer. In the case of too-short spacers, the advantages due to the increased DNA affinity are canceled due to the incorrect positioning of the reactive group, thus leading to cleavage inhibition.
设计了一系列顺 - 顺 - 三氨基环己烷锌（II）配合物 - 蒽醌嵌入剂共轭物，以便于其合成和修饰，已将其作为质粒DNA的水解切割剂进行了研究。配体结构包括通过不同长度（从C(4)到C(8)）的烷基间隔基连接到可嵌入DNA的蒽醌基团的三氨基环己烷平台。在5 microM的浓度下，具有C(8)烷基间隔基的衍生物配合物在pH 7和37摄氏度下以4.6×10(-6) s(-1)的速率诱导超螺旋DNA的水解链断裂。与缺乏锌 - 三氨基环己烷配合物的蒽醌相比，金属配合物与蒽醌基团的共轭导致切割效率提高了15倍。所采用的直接合成方法允许系统地改变间隔基长度，从而有可能更深入地了解嵌入基团在确定体系反应性中的作用。不同配合物反应性的比较表明，随着间隔基长度的增加，DNA切割效率显著提高。在间隔基过短的情况下，由于反应基团定位不正确，DNA亲和力增加带来的优势被抵消，从而导致切割抑制。
