Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 58, Issue 42, Pages 14929-14934Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201907816
Keywords
DNA probe; host-guest systems; nanopore; simultaneous quantification; single-molecule studies
Categories
Funding
- Ministry of Science and Technology of China [2016YFA0203200]
- National Natural Science Foundation of China [21974144, 31571010, 21874136]
- Institute of Chemistry, Chinese Academy of Sciences
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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 alpha-hemolysin (alpha HL). 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 alpha HL 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.
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