Tricolour fluorescence detection of sequence-specific DNA with a new molecular beacon and a nucleic acid dye TOTO-3

Analyst. 2012 Dec 21;137(24):5898-905. doi: 10.1039/c2an35910c.

Abstract

We have developed a tricolor fluorescence quantitative method for sequence-specific DNA detection using a new molecular beacon (MB) and a nucleic acid dye TOTO-3. This new MB is designed with two fluorophores of FAM and TAMRA instead of one fluorophore and one quencher of traditional MB, and a nucleotide with guanine base is attached directly to FAM as a quencher. In the absence of target DNA, MBs are in the stem-loop state. The fluorescence of FAM is absorbed by TAMRA, and the fluorescence of TAMRA is quenched by guanine base. Meanwhile, the interaction between TOTO-3 and MBs is very weak. In the presence of target DNA, MBs hybridize with target DNA to form a double-stranded structure. TAMRA is separated from FAM and guanine base, and the fluorescence of FAM and TAMRA recovers simultaneously. At the same time TOTO-3 binds to double-stranded DNA, the fluorescence of TOTO-3 significantly enhances. In this strategy, the false-positive signals of MBs caused by non-specific interactions can be distinguished by the change of the ratio of the total fluorescence intensities of FAM and TAMRA to that of TOTO-3 at different concentrations of target DNA. In the simple sample, the detection of target DNA can be achieved with the total fluorescence intensity of three dyes, which results in a significant improvement of the detection sensitivity. In the complex sample, the detection of target DNA can be achieved with the fluorescence intensity of TOTO-3 which can overcome the false-positive signals of MBs and improve the detection accuracy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Buffers
  • Color
  • DNA / analysis*
  • DNA / chemistry
  • DNA / genetics*
  • Fluorescent Dyes / chemistry*
  • Hydrogen-Ion Concentration
  • Limit of Detection
  • Nucleic Acid Hybridization
  • Oligonucleotide Probes / chemistry*
  • Oligonucleotide Probes / genetics
  • Osmolar Concentration
  • Polymorphism, Single Nucleotide
  • Quinolines / chemistry*
  • Spectrometry, Fluorescence / methods*
  • Temperature
  • Thiazoles / chemistry*

Substances

  • Buffers
  • Fluorescent Dyes
  • Oligonucleotide Probes
  • Quinolines
  • TOTO-3 compound
  • Thiazoles
  • DNA