Skov K A, Adomat H, Konway D C, Farrell N P
Chem Biol Interact. 1987;62(2):117-29. doi: 10.1016/0009-2797(87)90084-6.
A simple and rapid method has been used to compare the binding of platinum complexes to DNA, in a relatively qualitative manner. A compound bound at or near the restriction site inhibits enzymatic cleavage of DNA; inhibition of BamHI and EcoRI activity by complexes was assessed in this study using linearized pSV2-gpt plasmid. Our particular interest was in DNA binding by complexes of platinum (Pt) with known organic radiosensitizers (RS), to determine whether the Pt was able to target the RS to the DNA. Although the Pt-RS complexes investigated themselves have moderate radiosensitizing ability (like the inorganic complexes, cis- or trans-diamminedichloroplatinum(II), c- or t-DDP) none of the Pt-RS inhibit to the same extent as c- or t-DDP. However, there appears to be some correlation between enhanced radiosensitization by Pt-RS over Pt(RS)2, with the degree of Pt binding (as assessed by our assay). Our results using isolated DNA suggest that not all complexes bind well (e.g. Pt with two RS ligands), but that in certain cases (e.g. Pt with only one RS), it is possible to target the drug to the DNA. An ammine or amine ligand may be required in order to target a radiosensitizer to DNA using platinum.
一种简单快速的方法已被用于以相对定性的方式比较铂配合物与DNA的结合。在限制位点或其附近结合的化合物会抑制DNA的酶切；本研究中使用线性化的pSV2 - gpt质粒评估了配合物对BamHI和EcoRI活性的抑制作用。我们特别感兴趣的是铂（Pt）与已知有机放射增敏剂（RS）的配合物与DNA的结合，以确定Pt是否能够将RS靶向到DNA上。尽管所研究的Pt - RS配合物本身具有中等放射增敏能力（如无机配合物顺式或反式二氯二氨铂（II），c - 或t - DDP），但没有一种Pt - RS的抑制程度与c - 或t - DDP相同。然而，Pt - RS相对于Pt（RS）2增强的放射增敏作用与Pt的结合程度（通过我们的测定评估）之间似乎存在一些相关性。我们使用分离DNA的结果表明，并非所有配合物都能很好地结合（例如带有两个RS配体的Pt），但在某些情况下（例如仅带有一个RS的Pt），有可能将药物靶向到DNA上。为了使用铂将放射增敏剂靶向到DNA上，可能需要一个氨或胺配体。
