Molecular recognition of DNA by small molecules. Synthesis of bis(methidium)spermine, a DNA polyintercalating molecule

Abstract

The molecular recognition of DNA by small molecules is an important macromolecular receptor-drug interaction in the field of chemotherapy. The formation of noncovalently bound nucleic acid-drug complexes produces profound pharmacological effects by interfering with biological processes in which nucleic acids participate. The fact that DNA is a defined macromolecular receptor allows a rational approach to drug design and permits a unique opportunity for studying site-specific drug-binding processes. The therapeutic importance and the possibility for a detailed chemical understanding of the mechanism of action of these DNA-drug complexes provide sufficient stimulus to develop a rational methodology for optimizing the thermodynamics, kinetics, sequence specificity, structural specificity, and chemical specificity of these binding ligands.

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