Discriminating small molecule DNA binding modes by single molecule force spectroscopy

FEBS Letters

Pope, Lisa H.²  Krautbauer, Rupert¹  Allen, Stephanie²  Schrader, Tobias E.¹  Gaub, Hermann E.¹ 

[1] Lehrstuhl für Angewandte Physik and CeNS, Ludwig-Maximilians Universität, Amalienstr. 54, 80799 Munich, Germany;Laboratory of Biophysics and Surface Analysis, School of Pharmaceutical Sciences, The University of Nottingham, Nottingham NG7 2RD, UK

关键词: Force spectroscopy;    Single molecule;    DNA;    Small molecule binding;    Cisplatin;    Berenil;    Ethidium bromide;   

DOI  :  10.1016/S0014-5793(01)03257-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown