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Updated: Jan 28, 2026

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Direct Analysis of Incorporation of an Anticancer Drug into DNA at Single-Molecule Resolution

Takahito Ohshiro1, Yuuki Komoto1, Masamitsu Konno2

  • 1The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka, 567-0047, Japan.

Scientific Reports
|March 9, 2019
PubMed

Insights

Researchers developed a novel method to detect trifluridine (FTD) in DNA by measuring single-molecule electrical conductance. This breakthrough allows direct observation of drug incorporation, aiding anticancer drug development.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Nanotechnology

Background:

  • Identifying the precise location of anticancer drug incorporation into DNA is crucial for understanding drug mechanisms.
  • Current methods lack the sensitivity to directly confirm drug-DNA interactions at the molecular level.
  • Trifluridine (FTD) is an anticancer agent suspected to incorporate into DNA, but this has not been experimentally verified.

Purpose of the Study:

  • To develop a method for directly detecting trifluridine (FTD) within single-stranded DNA molecules.
  • To confirm the incorporation of FTD into DNA sequences.
  • To establish a foundation for developing more effective DNA-targeting anticancer therapies.

Main Methods:

  • Utilized single-molecule electrical conductance measurements to differentiate between DNA nucleosides and incorporated FTD.
  • Analyzed the electrical conductance signatures of individual molecules to determine sequence composition.
  • Applied the method to 21-base single-stranded DNA sequences containing FTD.

Main Results:

  • Successfully detected and distinguished trifluridine (FTD) within single-stranded DNA at the single-molecule level.
  • Determined the complete sequence of 21-base single-stranded DNA, including the positions of incorporated FTD.
  • Provided the first direct experimental evidence of FTD incorporation into DNA.

Conclusions:

  • The developed electrical conductance method enables direct detection of drug incorporation into DNA.
  • This technique offers a powerful new tool for studying DNA-damaging anticancer agents like FTD.
  • The methodology has the potential to accelerate the development of novel and more effective anticancer drugs.

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