Sulfur incorporation into nucleic acids accelerates enzymatic activity

Hyun Shin, Jun Young Cho, Boyoung Y. Park, Cheulhee Jung

Research output: Contribution to journalArticlepeer-review


DNAzymes play a crucial role in biosensors for signal detection, but specific structures are required for diagnostic applications, complicating their design. This study reports a novel approach to the development of DNAzymes by incorporating sulfur atoms into nucleic acids via phosphorothioate (PS) bonds. Unlike traditional DNAzymes that rely on specific structures such as G-quadruplexes, this approach leads to high enzymatic activity without structural constraints. Computational analysis reveals that the change in the electron density of the nucleobases due to PS modification enhances interactions within the DNAzyme-H2O2-hemin complex, accelerating the rate-determining step and improving enzymatic activity. Systematic guidelines for the development of non-sequence constrained DNAzymes are provided by investigating the effect of the number of PS modifications, the length of the DNA, and various nucleobase combinations. α-thio-dNTP, a monomer containing PS, exhibits no observable enzymatic activity, but enzymatic activity is recorded for single-stranded DNA (ssDNA) containing PS. However, when the ssDNA is transformed into double-stranded DNA (dsDNA), the bases that react with hemin are blocked by hydrogen bonding, reducing enzymatic activity. An enzymogenic signaling system that differentiates between ssDNA and dsDNA is subsequently developed for sequence-specific colorimetric detection, demonstrating significant promise for overcoming the limitations of conventional DNAzymes in molecular diagnosis.

Original languageEnglish
Article number152548
JournalChemical Engineering Journal
Publication statusPublished - 2024 Aug 1

Bibliographical note

Publisher Copyright:
© 2024 Elsevier B.V.


  • Enzymogenic
  • Non-sequence constrained
  • Phosphorothioate
  • PS DNAzyme
  • Sequence-specific signaling
  • Sulfur incorporation

ASJC Scopus subject areas

  • General Chemistry
  • Environmental Chemistry
  • General Chemical Engineering
  • Industrial and Manufacturing Engineering


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