Drug-DNA Interaction---Base Sequence Selectivity

DNA与各种小分子相互作用，包括抗生素、致癌因子和生物染色剂。其中许多已经被开发成药物。这种相互作用的详细分子和电子机制的阐明已经被尝试，因为它被认为是必不可少的，不仅对药物化学本身的发展，而且对建立基因解码相互作用的有用例子。药物或相关小分子也可以看作是其核酸结合位点附近存在的力场的化学探针。通过紫外光谱、荧光光谱、红外光谱、拉曼光谱进行了广泛的研究。圆二色性、核磁共振、停流、电泳、电镜和流动二色性实验表明，存在两种可区分的结合模式：堆叠基间插层（B1）和凹槽结合（B2）。然而，除了这种牢固的结合外，每种药物都有松散的相互作用(E)，可以通过荧光变化来检测。一般来说，E与GC部分的相互作用强于与AT部分的相互作用。对于B1， GC b> AT，对于B2， GC<AT。在我们的拉曼研究过程中，发现了一个有趣的事实，即沿双螺旋DNA链从嵌入位点（GC, B1）转移到凹槽结合位点（AT, B2），一个水溶性铜卟啉通过嵌入在GC部分结合，但在激光照射下它进入ATAT凹槽。

DNA interacts with a variety of smaller molecules including antibiotics, calcinogens and biological stains. Many of these have been developed as drugs. Elucidation of the detailed molecular and electronic mechanisms of such interactions has been attempted, because it is considered to be essential, not only for the development of drug chemistry itself, but also for establishing useful examples of gene decoding interactions. A drug or related small molecule can also be regarded as a chemical probe of the force field existing in the vicinity of its nucleic acid binding site.Extensive studies by means of ultraviolet spectroscopy, fluorescence spectroscopy, infrared spectroscopy, Raman spectroscopy. circular dichroism, and NMR, in combination with stopped flow, electrophoresis, electron microscopy, and flow dichroism experiments, have shown that there are two modes of binding distinguish-able : intercalation between stacked bases (B1) and groove binding (B2). Besides such firm bindings, however, every drug has been found to have a loose interaction (E) which can be detected through a fluorescence change. It has been found that in general the E interaction is stronger with the GC portion than with the AT portion. For B1, GC>AT, and for B2, GC<AT.In the course of our Raman study, an interesting fact has been found which indicates the translocation of a legand from an intercalation site (GC, B1) into a groove-binding site (AT, B2) along the double-helical DNA chain, A water soluble Cu-porphyrin binds through an intercalation at a GC portion, but on a laser irradiation it goes into an ATAT groove.