Nanopore Discrimination of Coagulation Biomarker Derivatives and Characterization of a Post-Translational Modification
One of the most important health challenges is the early and ongoing detection of disease for prevention, as well as personalized treatment management. Development of new sensitive analytical point-of-care tests are, therefore, necessary for direct biomarker detection from biofluids as critical tool...
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| Veröffentlicht in: | ACS central science 2023-02, Vol.9 (2), p.228-238 |
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| creator | Stierlen, Aïcha Greive, Sandra J. Bacri, Laurent Manivet, Philippe Cressiot, Benjamin Pelta, Juan |
| description | One of the most important health challenges is the early and ongoing detection of disease for prevention, as well as personalized treatment management. Development of new sensitive analytical point-of-care tests are, therefore, necessary for direct biomarker detection from biofluids as critical tools to address the healthcare needs of an aging global population. Coagulation disorders associated with stroke, heart attack, or cancer are defined by an increased level of the fibrinopeptide A (FPA) biomarker, among others. This biomarker exists in more than one form: it can be post-translationally modified with a phosphate and also cleaved to form shorter peptides. Current assays are long and have difficulties in discriminating between these derivatives; hence, this is an underutilized biomarker for routine clinical practice. We use nanopore sensing to identify FPA, the phosphorylated FPA, and two derivatives. Each of these peptides is characterized by unique electrical signals for both dwell time and blockade level. We also show that the phosphorylated form of FPA can adopt two different conformations, each of which have different values for each electrical parameter. We were able to use these parameters to discriminate these peptides from a mix, thereby opening the way for the potential development of new point-of-care tests. |
| doi_str_mv | 10.1021/acscentsci.2c01256 |
| format | Article |
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Development of new sensitive analytical point-of-care tests are, therefore, necessary for direct biomarker detection from biofluids as critical tools to address the healthcare needs of an aging global population. Coagulation disorders associated with stroke, heart attack, or cancer are defined by an increased level of the fibrinopeptide A (FPA) biomarker, among others. This biomarker exists in more than one form: it can be post-translationally modified with a phosphate and also cleaved to form shorter peptides. Current assays are long and have difficulties in discriminating between these derivatives; hence, this is an underutilized biomarker for routine clinical practice. We use nanopore sensing to identify FPA, the phosphorylated FPA, and two derivatives. Each of these peptides is characterized by unique electrical signals for both dwell time and blockade level. We also show that the phosphorylated form of FPA can adopt two different conformations, each of which have different values for each electrical parameter. We were able to use these parameters to discriminate these peptides from a mix, thereby opening the way for the potential development of new point-of-care tests.</description><identifier>ISSN: 2374-7943</identifier><identifier>ISSN: 2374-7951</identifier><identifier>EISSN: 2374-7951</identifier><identifier>DOI: 10.1021/acscentsci.2c01256</identifier><identifier>PMID: 36844502</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Biomarkers ; Cancer ; Chemical Sciences ; Coagulation ; Discrimination ; Dwell time ; Heart attacks ; Mass spectrometry ; Mathematical analysis ; Myocardial infarction ; Parameters ; Peptides ; Phosphorylation ; Post-translation ; Proteins ; Scientific imaging ; Sensors ; Thrombosis</subject><ispartof>ACS central science, 2023-02, Vol.9 (2), p.228-238</ispartof><rights>2023 The Authors. Published by American Chemical Society</rights><rights>2023 The Authors. Published by American Chemical Society.</rights><rights>2023. This work is licensed under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>2023 The Authors. 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Current assays are long and have difficulties in discriminating between these derivatives; hence, this is an underutilized biomarker for routine clinical practice. We use nanopore sensing to identify FPA, the phosphorylated FPA, and two derivatives. Each of these peptides is characterized by unique electrical signals for both dwell time and blockade level. We also show that the phosphorylated form of FPA can adopt two different conformations, each of which have different values for each electrical parameter. 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| subjects | Biomarkers Cancer Chemical Sciences Coagulation Discrimination Dwell time Heart attacks Mass spectrometry Mathematical analysis Myocardial infarction Parameters Peptides Phosphorylation Post-translation Proteins Scientific imaging Sensors Thrombosis |
| title | Nanopore Discrimination of Coagulation Biomarker Derivatives and Characterization of a Post-Translational Modification |
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