[DNA intercalators: their interaction with DNA and other cell components and their use in biological research]

DNA intercalators include aromatic heterocyclic compounds of various chemical classes with profound biological activities. The flat molecules of these ligands intercalate between base pairs of DNA right-handed helix, lengthening and unwinding this structure at the intercalation sites. Lerman first postulated the intercalation model for complexes of native DNA with acridine derivatives. The structures of intercalative complexes were further confirmed by the X-ray diffraction method. Besides, other physico-chemical criteria of DNA intercalation are as following: the increase in the contour length of duplex DNA; unwinding of supercoils from natural supercoiled covalently closed duplex DNA; the increase in Tm of DNA in the complexes with ligands. The changes of spectral properties of bounded ligands are also observed for DNA-intercalating agents. Various experimental methods are based on changes in the properties of nucleic acid structures and ligands due to DNA intercalation, including the fluorescent determination of nucleic acid structures and quantities; fluorescent assays of activities of various enzymes involved in nucleic acid metabolism; chromosome identification according to their fluorescent banding patterns; separation of nucleic acid topological forms, and many other methods. The inhibition of reactions of DNA replication, transcription, topoisomerization and of enzymatic degradation by DNA intercalators represents an important consequence of DNA structure modification due to intercalation. Besides, as hydrophobic cations DNA intercalators uncouple the oxidative phosphorylation in mammalian cell mitochondria. There are some other protein and phospholipid targets for DNA-intercalators in vivo. The intracellular distribution of these agents appear to be a very complicated selective process. These data point to the importance of application of DNA intercalators in pharmacology.