Identification and Characterization of DNA-Oxaliplatin Adducts through α-hemolysin Nanopores

Anal Chem. 2023 Aug 1;95(30):11201-11210. doi: 10.1021/acs.analchem.3c00461. Epub 2023 Jul 7.

Abstract

The antitumor effect of Pt-based drugs is determined by their binding activity with deoxyribonucleic acid (DNA), and understanding the reaction process in a systematic manner is crucial. However, existing assays used for DNA-Pt research suffer from several issues, such as complicated sample preparation, preamplification, and expensive instruments, which dramatically limit their practical application. In this study, a novel method was presented to investigate the adducts of DNA and oxaliplatin using an α-hemolysin nanopore sensor. This approach allows for real-time monitoring of the DNA-oxaliplatin condensation process through the detection of nanopore events associated with DNA-oxaliplatin adducts. Specifically, type I and II signals exhibiting specific current characteristics were observed during the process. Typical signals with high frequency were obtained by recording the designed DNA sequence. Furthermore, the production of these signals was confirmed to be independent of homologous adducts. This finding suggests that the DNA-oxaliplatin adduct can serve as a potential sensor for detecting oxaliplatin lesions and multiple types of molecules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / metabolism
  • DNA Adducts
  • Hemolysin Proteins
  • Nanopores*
  • Organoplatinum Compounds / chemistry
  • Organoplatinum Compounds / metabolism
  • Oxaliplatin

Substances

  • Oxaliplatin
  • Antineoplastic Agents
  • Hemolysin Proteins
  • DNA Adducts
  • Organoplatinum Compounds