Scanning probe visualization of electrostatically immobilized intercalating drug-nucleic acid complexes

DNA intercalators are planar molecules that insert between the base pairs of duplex DNA. Intercalation into DNA necessarily results in changes in DNA conformation, separating base pairs along the helical axis; thus, intercalators are of great importance as probes of nucleic acid structure and as interferents of DNA replication, transcription, and/or topoisomerase activities. Relationships between structures of intercalators and the changes they cause in DNA conformation are subtle and remain unresolved. An intercalating drug molecule has been synthesized that incorporates markers easily distinguished by atomic force microscopy ~AFM!. This specially designed psoralen derivative has been intercalated into DNA. To facilitate recognition of the point of intercalation, the psoralen derivative contained a biotin moiety that was exposed and bound readily to streptavidin-coated colloidal gold beads. Atomic force micrographs were obtained following electrostatic immobilization of the DNA/psoralen complexes onto mica surfaces. This article presents AFM images of intercalating drug–DNA complexes which may provide further data for the study of structure/intercalator relationships. © 1995 American Vacuum Society.