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A Dual‐Response DNA Probe for Simultaneously Monitoring Enzymatic Activity and Environmental pH Using a Nanopore
Author(s) -
Liu Lei,
You Yi,
Zhou Ke,
Guo Bingyuan,
Cao Zhong,
Zhao Yuliang,
Wu HaiChen
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201907816
Subject(s) - nanopore , protease , chemistry , dna , nanosensor , biophysics , biochemistry , peptide , enzyme , nanopore sequencing , nanotechnology , phenylalanine , combinatorial chemistry , dna sequencing , biology , materials science , amino acid
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.