title: Discriminating small molecule DNA binding modes by single molecule force spectroscopy.
abstract: 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.
authors.affiliation: Lehrstuhl für Angewandte Physik and CeNS, Luwig-Maximilians Universität, Munich, Germany.
authors.forename: Rupert
authors.initials: R
authors.lastname: Krautbauer
authors.forename: Lisa H
authors.initials: LH
authors.lastname: Pope
authors.forename: Tobias E
authors.initials: TE
authors.lastname: Schrader
authors.forename: Stephanie
authors.initials: S
authors.lastname: Allen
authors.forename: Hermann E
authors.initials: HE
authors.lastname: Gaub
mesh_terms: D010582:Bacteriophage lambda / Q000737:chemistry; D002945:Cisplatin / Q000737:chemistry* / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000494:pharmacology; D004279:DNA, Viral / Q000737:chemistry*; D004133:Diminazene / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D004996:Ethidium / Q000737:chemistry* / Q000494:pharmacology; D007364:Intercalating Agents / Q000737:chemistry / Q000494:pharmacology; D018625:Microscopy, Atomic Force / Q000379:methods; D009690:Nucleic Acid Conformation / Q000187:drug effects; D013314:Stress, Mechanical
chemical_list: D003432:Cross-Linking Reagents; D004279:DNA, Viral; D007364:Intercalating Agents; D004996:Ethidium; C003915:diminazene aceturate; D002945:Cisplatin; D004133:Diminazene