Discriminating small molecule DNA binding modes by single molecule force spectroscopy

• Published in: FEBS letters Vol. 510; no. 3; pp. 154 - 158
• Main Authors: Krautbauer, Rupert, Pope, Lisa H., Schrader, Tobias E., Allen, Stephanie, Gaub, Hermann E.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 16.01.2002
• Subjects: Bacteriophage lambda - chemistry; Berenil; Cisplatin; Cisplatin - chemistry; Cisplatin - pharmacology; Cross-Linking Reagents - chemistry; Cross-Linking Reagents - pharmacology; Diminazene - analogs & derivatives; Diminazene - chemistry; Diminazene - pharmacology; DNA; DNA, Viral - chemistry; Ethidium - chemistry; Ethidium - pharmacology; Ethidium bromide; Force spectroscopy; Intercalating Agents - chemistry; Intercalating Agents - pharmacology; Microscopy, Atomic Force - methods; Nucleic Acid Conformation - drug effects; Single molecule; Small molecule binding; Stress, Mechanical; Berenil; Ethidium bromide; Force spectroscopy; DNA; Small molecule binding; Cisplatin; Single molecule
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(01)03257-4

Drugs may interact with double stranded DNA via a variety of binding modes, each mode giving rise to a specific pharmacological function. Here we demonstrate the ability of single molecule force spectroscopy to discriminate between different interaction modes by measuring the mechanical properties of DNA and their modulation upon the binding of small molecules. Due to the unique topology of double stranded DNA and due to its base pair stacking pattern, DNA undergoes several well-characterised structural transitions upon stretching. We show that small molecule binding markedly affects these transitions in ways characteristic to the binding mode and that these effects can be detected at the level of an individual molecule. The minor groove binder berenil, the crosslinker cisplatin and the intercalator ethidium bromide are compared.