Fluorescent probes for monitoring myeloperoxidase-derived hypochlorous acid: a comparative study
Abstract MPO-derived oxidants including HOCl contribute to tissue damage and the initiation and propagation of inflammatory diseases. The search for small molecule inhibitors of myeloperoxidase, as molecular tools and potential drugs, requires the application of high throughput screening assays base...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-13317-8 |
| _version_ | 1811243553378009088 |
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| author | Karolina Pierzchała Marlena Pięta Monika Rola Małgorzata Świerczyńska Angelika Artelska Karolina Dębowska Radosław Podsiadły Jakub Pięta Jacek Zielonka Adam Sikora Andrzej Marcinek Radosław Michalski |
| author_facet | Karolina Pierzchała Marlena Pięta Monika Rola Małgorzata Świerczyńska Angelika Artelska Karolina Dębowska Radosław Podsiadły Jakub Pięta Jacek Zielonka Adam Sikora Andrzej Marcinek Radosław Michalski |
| author_sort | Karolina Pierzchała |
| collection | DOAJ |
| description | Abstract MPO-derived oxidants including HOCl contribute to tissue damage and the initiation and propagation of inflammatory diseases. The search for small molecule inhibitors of myeloperoxidase, as molecular tools and potential drugs, requires the application of high throughput screening assays based on monitoring the activity of myeloperoxidase. In this study, we have compared three classes of fluorescent probes for monitoring myeloperoxidase-derived hypochlorous acid, including boronate-, aminophenyl- and thiol-based fluorogenic probes and we show that all three classes of probes are suitable for this purpose. However, probes based on the coumarin fluorophore turned out to be not reliable indicators of the inhibitors’ potency. We have also determined the rate constants of the reaction between HOCl and the probes and they are equal to 1.8 × 104 M−1s−1 for coumarin boronic acid (CBA), 1.1 × 104 M−1s−1 for fluorescein based boronic acid (FLBA), 3.1 × 104 M−1s−1 for 7-(p-aminophenyl)-coumarin (APC), 1.6 × 104 M−1s−1 for 3’-(p-aminophenyl)-fluorescein (APF), and 1 × 107 M−1s−1 for 4-thiomorpholino-7-nitrobenz-2-oxa-1,3-diazole (NBD-TM). The high reaction rate constant of NBD-TM with HOCl makes this probe the most reliable tool to monitor HOCl formation in the presence of compounds showing HOCl-scavenging activity. |
| first_indexed | 2024-04-12T14:09:23Z |
| format | Article |
| id | doaj.art-0d0c54d8360f4776869e515cc662ed47 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T14:09:23Z |
| publishDate | 2022-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-0d0c54d8360f4776869e515cc662ed472022-12-22T03:29:56ZengNature PortfolioScientific Reports2045-23222022-06-0112111410.1038/s41598-022-13317-8Fluorescent probes for monitoring myeloperoxidase-derived hypochlorous acid: a comparative studyKarolina Pierzchała0Marlena Pięta1Monika Rola2Małgorzata Świerczyńska3Angelika Artelska4Karolina Dębowska5Radosław Podsiadły6Jakub Pięta7Jacek Zielonka8Adam Sikora9Andrzej Marcinek10Radosław Michalski11Department of Chemistry, Institute of Applied Radiation Chemistry, Lodz University of TechnologyDepartment of Chemistry, Institute of Applied Radiation Chemistry, Lodz University of TechnologyDepartment of Chemistry, Institute of Applied Radiation Chemistry, Lodz University of TechnologyDepartment of Chemistry, Institute of Polymer and Dye Technology, Lodz University of TechnologyDepartment of Chemistry, Institute of Applied Radiation Chemistry, Lodz University of TechnologyDepartment of Chemistry, Institute of Applied Radiation Chemistry, Lodz University of TechnologyDepartment of Chemistry, Institute of Polymer and Dye Technology, Lodz University of TechnologyDepartment of Chemistry, Institute of Applied Radiation Chemistry, Lodz University of TechnologyDepartment of Biophysics and Free Radical Research Center, Medical College of WisconsinDepartment of Chemistry, Institute of Applied Radiation Chemistry, Lodz University of TechnologyDepartment of Chemistry, Institute of Applied Radiation Chemistry, Lodz University of TechnologyDepartment of Chemistry, Institute of Applied Radiation Chemistry, Lodz University of TechnologyAbstract MPO-derived oxidants including HOCl contribute to tissue damage and the initiation and propagation of inflammatory diseases. The search for small molecule inhibitors of myeloperoxidase, as molecular tools and potential drugs, requires the application of high throughput screening assays based on monitoring the activity of myeloperoxidase. In this study, we have compared three classes of fluorescent probes for monitoring myeloperoxidase-derived hypochlorous acid, including boronate-, aminophenyl- and thiol-based fluorogenic probes and we show that all three classes of probes are suitable for this purpose. However, probes based on the coumarin fluorophore turned out to be not reliable indicators of the inhibitors’ potency. We have also determined the rate constants of the reaction between HOCl and the probes and they are equal to 1.8 × 104 M−1s−1 for coumarin boronic acid (CBA), 1.1 × 104 M−1s−1 for fluorescein based boronic acid (FLBA), 3.1 × 104 M−1s−1 for 7-(p-aminophenyl)-coumarin (APC), 1.6 × 104 M−1s−1 for 3’-(p-aminophenyl)-fluorescein (APF), and 1 × 107 M−1s−1 for 4-thiomorpholino-7-nitrobenz-2-oxa-1,3-diazole (NBD-TM). The high reaction rate constant of NBD-TM with HOCl makes this probe the most reliable tool to monitor HOCl formation in the presence of compounds showing HOCl-scavenging activity.https://doi.org/10.1038/s41598-022-13317-8 |
| spellingShingle | Karolina Pierzchała Marlena Pięta Monika Rola Małgorzata Świerczyńska Angelika Artelska Karolina Dębowska Radosław Podsiadły Jakub Pięta Jacek Zielonka Adam Sikora Andrzej Marcinek Radosław Michalski Fluorescent probes for monitoring myeloperoxidase-derived hypochlorous acid: a comparative study Scientific Reports |
| title | Fluorescent probes for monitoring myeloperoxidase-derived hypochlorous acid: a comparative study |
| title_full | Fluorescent probes for monitoring myeloperoxidase-derived hypochlorous acid: a comparative study |
| title_fullStr | Fluorescent probes for monitoring myeloperoxidase-derived hypochlorous acid: a comparative study |
| title_full_unstemmed | Fluorescent probes for monitoring myeloperoxidase-derived hypochlorous acid: a comparative study |
| title_short | Fluorescent probes for monitoring myeloperoxidase-derived hypochlorous acid: a comparative study |
| title_sort | fluorescent probes for monitoring myeloperoxidase derived hypochlorous acid a comparative study |
| url | https://doi.org/10.1038/s41598-022-13317-8 |
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