Yamamoto Yoji, Tsuboi Wataru, Komiyama Makoto
Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan.
Nucleic Acids Res. 2003 Aug 1;31(15):4497-502. doi: 10.1093/nar/gkg634.
Oligoamines (spermidine, dipropylenetriamine and propylenediamine) were covalently attached to acridine via a hexamethylene linker. These oligoamine-acridine conjugates were efficiently bound to gap sites in substrate DNA, and promoted the DNA hydrolysis by a homogeneous Ce(IV)/ethylenediamine-N,N,N',N'-tetraacetate (EDTA) complex at these sites. In contrast, the hydrolysis of the double-stranded portion in the DNA was little affected by these conjugates, although they were strongly bound thereto by the intercalation of their acridine moieties. As a result, the gap site was selectively and efficiently hydrolyzed by combining the Ce(IV)/EDTA complex with the oligoamine--acridine conjugate. Either the oligoamine or the acridine was only poorly active for the purpose, substantiating the essential role of cooperation between them. The promotion of gap-selective DNA hydrolysis by the conjugates has been ascribed to electrostatic stabilization of a negatively charged transition state by their positive charges.
低聚胺(亚精胺、二亚丙基三胺和丙二胺)通过六亚甲基连接基与吖啶共价连接。这些低聚胺 - 吖啶共轭物能有效地结合到底物DNA的缺口位点,并促进在这些位点由均相铈(IV)/乙二胺 - N,N,N',N'-四乙酸(EDTA)络合物介导的DNA水解。相比之下,DNA双链部分的水解几乎不受这些共轭物的影响,尽管它们通过吖啶部分的嵌入而与之紧密结合。结果,通过将铈(IV)/EDTA络合物与低聚胺 - 吖啶共轭物相结合,缺口位点被选择性且高效地水解。单独的低聚胺或吖啶对此目的的活性都很差,这证实了它们之间协同作用的重要性。共轭物对缺口选择性DNA水解的促进作用归因于其正电荷对带负电过渡态的静电稳定作用。