Drug-DNA Interaction---Base Sequence Selectivity

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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.