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DNA-Binding of Drugs Used in Medicinal Therapies

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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 DNA-toroids and the formation of micronuclei in tissues will be interpreted.
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Keywords: 4-hydroxyphenyl ring; DNA-Binding; Ec hinomycin; Groove Binding; Pa clitaxe l; daunomycin derivative

Document Type: Review Article

Publication date: 2002-02-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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