Mirabelli C K, Sung C M, Zimmerman J P, Hill D T, Mong S, Crooke S T
Biochem Pharmacol. 1986 May 1;35(9):1427-33. doi: 10.1016/0006-2952(86)90106-1.
The interactions of certain gold(I) and gold(III) complexes with isolated plasmid pBR322 DNA were defined and compared to those of cis-diamminedichloroplatinum(II), CDDP, using an agarose gel electrophoresis assay. Trichloro(pyridine)gold(III) appeared to bind to DNA as evidenced by its ability to produce dose-dependent changes in the electrophoretic mobilities of closed circular, supercoiled, closed circular, relaxed, and open circular plasmid DNAs. These effects suggest that the gold containing complex induces conformational changes in the plasmid as a result of the compound binding to the DNA and the subsequent unwinding of the double helix and shorting of the DNA. Auranofin [(2,3,4,6-tetra-O-acetyl-1-thio-beta-D-glucopyranosato-S)-triethyl phosphine gold(I)] did not appear to interact with DNA under any conditions. However, its analog chloro(triethylphosphine) gold(I) interacted with DNA at pH 9.5 in borate buffer and produced electrophoretic mobility changes in pBR322 DNA which were different from those produced by the gold(III) complexes that were evaluated. Binding of chloro(triethylphosphine) gold(I) was inhibited by the co-addition of the thiosugar portion of auranofin suggesting preferential binding of the gold moiety to thiosugar, which results in the production of auranofin (or a sugar containing) gold complex and inhibition of gold binding to DNA. The interactions of a number of gold compounds with DNA were also evidenced by their abilities to inhibit the binding of ethidium bromide to DNA. The results from these studies indicate that: gold containing complexes can bind to, and produce conformational changes in, DNA; gold(I) and gold(III) complexes may interact with DNA via different chemical mechanisms to produce different conformational changes in DNA; and certain coordinating ligands in gold complexes (e.g. Cl, Br and SCN) can be exchanged for binding sites on DNA by gold.
使用琼脂糖凝胶电泳分析法，确定了某些金（I）和金（III）配合物与分离的质粒pBR322 DNA的相互作用，并将其与顺二氯二氨铂（II）（CDDP）的相互作用进行了比较。三氯（吡啶）金（III）似乎能与DNA结合，这可由其使闭环、超螺旋、闭环、松弛和开环质粒DNA的电泳迁移率产生剂量依赖性变化的能力得到证明。这些效应表明，含金配合物由于与DNA结合以及随后双螺旋解旋和DNA缩短，从而诱导质粒发生构象变化。在任何条件下，金诺芬[（2,3,4,6 - 四 - O - 乙酰基 - 1 - 硫代 - β - D - 吡喃葡萄糖酸 - S）- 三乙膦金（I）]似乎都不与DNA相互作用。然而，其类似物氯（三乙膦）金（I）在硼酸盐缓冲液pH 9.5时与DNA相互作用，并使pBR322 DNA的电泳迁移率发生变化，这种变化与所评估的金（III）配合物产生的变化不同。氯（三乙膦）金（I）的结合会因同时添加金诺芬的硫糖部分而受到抑制，这表明金部分优先与硫糖结合，从而导致生成金诺芬（或含糖）金配合物，并抑制金与DNA的结合。多种金化合物与DNA的相互作用也可由它们抑制溴化乙锭与DNA结合的能力得到证明。这些研究结果表明：含金配合物能够与DNA结合并使其产生构象变化；金（I）和金（III）配合物可能通过不同的化学机制与DNA相互作用，从而在DNA中产生不同的构象变化；并且金配合物中的某些配位配体（如Cl、Br和SCN）可被金交换以占据DNA上的结合位点。
