Thermodynamic basis of the enhanced specificity of structured DNA probes

Proc Natl Acad Sci U S A. 1999 May 25;96(11):6171-6. doi: 10.1073/pnas.96.11.6171.

Abstract

Molecular beacons are DNA probes that form a stem-and-loop structure and possess an internally quenched fluorophore. When they bind to complementary nucleic acids, they undergo a conformational transition that switches on their fluorescence. These probes recognize their targets with higher specificity than probes that cannot form a hairpin stem, and they easily discriminate targets that differ from one another by only a single nucleotide. Our results show that molecular beacons can exist in three different states: bound to a target, free in the form of a hairpin structure, and free in the form of a random coil. Thermodynamic analysis of the transitions between these states reveals that enhanced specificity is a general feature of conformationally constrained probes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • DNA Probes / chemical synthesis
  • DNA Probes / chemistry*
  • Fluoresceins
  • Hot Temperature
  • Kinetics
  • Models, Chemical
  • Models, Molecular
  • Nucleic Acid Conformation*
  • Nucleic Acid Denaturation
  • Oligodeoxyribonucleotides / chemical synthesis
  • Oligodeoxyribonucleotides / chemistry*
  • Solutions
  • Thermodynamics

Substances

  • DNA Probes
  • Fluoresceins
  • Oligodeoxyribonucleotides
  • Solutions