Small-molecule binding at an abasic site of DNA: Strong binding of lumiflavin for improved recognition of thymine-related single nucleotide polymorphisms

N. B. Sankaran, Yusuke Sato, Fuyuki Sato, Burki Rajendar, Kotaro Morita, Takehiro Seino, Seiichi Nishizawa, Norio Teramae

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1522-1529
Number of pages8
JournalJournal of Physical Chemistry B
Volume113
Issue number5
DOIs
Publication statusPublished - 2009 Feb 5

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

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