DNA-binding of Drugs Used in Medicinal Therapies
Pp. 619-645 (27)
G. Bischoff, S. Hoffmann and R. Zhdanov
The interactions of various low-molecular weight substances with DNA are naturally relevant mechanisms in the cellular cycle and so also used in medicinal treatment. Depending on the particular drug structure, DNA-binding modes like groove-binding, intercalating and/or stacking, give rise to supramolecular assemblies of the polynucleotides, as well as influence the DNA-protein binding.
In this review, we compare the underlying molecular structures, including general aspects of DNA sequences, with the benefit in medicinal treatment. While so far interest in this field had mainly been devoted to isolated nucleic acid/drug interactions, the present paper will focus on drug efficiencies generating and influencing supramolecular organizations and their complex sequence-dependent structure-activity codes. In particular, the attention will be directed to stereoelectronic relationships. Spatial enantioselective properties are discussed in details. As examples, the drug self-assemblies, as well as the influence of drugs on supramolecular DNA formations are described. A hypothetical connection between drug-influenced DNAtoroids and the formation of micronuclei in tissues will be interpreted. As an important group of medicines a variety of lipids appears, which could also be bound to chromatin and DNA as an individual molecules or as lipoproteins. Their upcoming importance on the regulation of lipid composition in genome, called lipidomics, is briefly described, too.
Martin Luther University Halle-Wittenberg, Department of Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany