Synthetic Biomarker Design by Using Analyte‐Responsive Acetaminophen

The use of synthetic biomarkers is an emerging technique to improve disease diagnosis. Here, we report a novel design strategy that uses analyte‐responsive acetaminophen (APAP) to expand the catalogue of analytes available for synthetic biomarker development. As proof‐of‐concept, we designed hydroge...

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Bibliographic Details
Published in:Chembiochem : a European journal of chemical biology 2017-05, Vol.18 (10), p.910-913
Main Authors: Nishihara, Tatsuya, Inoue, Joe, Tabata, Sho, Murakami, Shinnosuke, Ishikawa, Takamasa, Saito, Natsumi, Fukuda, Shinji, Tomita, Masaru, Soga, Tomoyoshi
Format: Article
Language:English
Subjects:
Acetaminophen
Acetaminophen - metabolism
Analgesics
Analgesics, Non-Narcotic - metabolism
Animal research
Animals
Biomarkers
Biomarkers - metabolism
Cells, Cultured
Chromatography, Liquid
Design analysis
Design improvements
Hydrogen peroxide
Hydrogen Peroxide - metabolism
In vivo methods and tests
Lipopolysaccharides - pharmacology
liquid chromatography
Liver - drug effects
Liver - metabolism
mass spectrometry
Mice
Oxidants - metabolism
synthetic biomarker
Tandem Mass Spectrometry
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Summary:The use of synthetic biomarkers is an emerging technique to improve disease diagnosis. Here, we report a novel design strategy that uses analyte‐responsive acetaminophen (APAP) to expand the catalogue of analytes available for synthetic biomarker development. As proof‐of‐concept, we designed hydrogen peroxide (H2O2)‐responsive APAP (HR‐APAP) and succeeded in H2O2 detection with cellular and animal experiments. In fact, for blood samples following HR‐APAP injection, we demonstrated that the plasma concentration ratio [APAP+APAP conjugates]/[HR‐APAP] accurately reflects in vivo differences in H2O2 levels. We anticipate that our practical methodology will be broadly useful for the preparation of various synthetic biomarkers. In vivo detection of an analyte from blood: Analyte‐responsive acetaminophen (APAP) can be used to estimate disease‐associated analyte levels from an in vivo conversion index. As proof‐of‐concept, hydrogen peroxide‐responsive APAP (HR‐APAP) enabled in vivo H2O2 analysis from a blood sample following HR‐APAP injection.
ISSN:1439-4227
1439-7633
DOI:10.1002/cbic.201700023