A Dual-Response DNA Probe for Simultaneously Monitoring Enzymatic Activity and Environmental pH Using a Nanopore

Lei Liu, Yi You, Ke Zhou, Bingyuan Guo, Zhong Cao, Yuliang Zhao, Hai Chen Wu

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Both protease overexpression and local pH changes are key signatures of cancer. However, the sensitive detection of protease activities and the accurate measurement of pH in a tumor environment remain challenging. Here, we develop a dual-response DNA probe that can simultaneously monitor protease activities and measure the local pH by translocation through α-hemolysin (αHL). The DNA probe bears a short peptide containing phenylalanine at a pre-designed position. Enzymatic cleavage of the peptide either exposes or removes the N-terminal phenylalanine that can form a complex with cucurbit[7]uril. Translocation of the DNA hybrid through αHL generates current signatures that can be used to quantify protease activities. Furthermore, the current signatures possess a pH-dependent pattern that reflects the local pH. Our results demonstrate that the versatile DNA probe may be further explored for simultaneously measuring multiple parameters of a complex system such as single cells in the future.

Original languageEnglish (US)
Pages (from-to)14929-14934
Number of pages6
JournalAngewandte Chemie - International Edition
Volume58
Issue number42
DOIs
StatePublished - Oct 14 2019

Keywords

  • DNA probe
  • host–guest systems
  • nanopore
  • simultaneous quantification
  • single-molecule studies

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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