Small-Molecule Binding at an Abasic Site of DNA: Strong Binding of Lumiflavin for Improved Recognition of Thymine-Related Single Nucleotide Polymorphisms

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• 作者：N. B. Sankaran ; Yusuke Sato ; Fuyuki Sato ; Burki Rajendar ; Kotaro Morita ; Takehiro Seino ; Seiichi Nishizawa ; Norio Teramae
• 刊名：Journal of Physical Chemistry B
• 出版年：2009
• 出版时间：February 5, 2009
• 年：2009
• 卷：113
• 期：5
• 页码：1522-1529
• 全文大小：215K
• 年卷期：v.113,no.5(February 5, 2009)
• ISSN：1520-5207

文摘

The binding behavior of lumiflavin, a biologically vital ligand, with DNA duplexes containing an abasic (AP) site and various target nucleobases opposite the AP site is studied. Lumiflavin binds selectively to thymine (T) opposite the AP site in a DNA duplex over other nucleobases. Using ¹H NMR spectroscopy and fluorescence measurements, we show that ligand−DNA complexation takes place by hydrogen-bond formation between the ligand and the target nucleobases and by stacking interactions between the ligand and the nucleobases flanking the AP site. From isothermal titration calorimetric experiments, we find that ligand incorporation into the AP sites is primarily enthalpy-driven. Examination of ionic strength dependency of ligand binding with DNA reveals that ligand−DNA complexation is a manifestation of both electrostatic and nonelectrostatic interactions and that the contribution from the nonelectrolyte effect is fundamental for the stabilization of the ligand−DNA complex. In comparison to riboflavin, reported previously as a T-selective ligand, lumiflavin binds to the DNA much more strongly and is a more promising ligand for efficient detection of T-related single nucleotide polymorphisms.