Discovery of Lithospermate B as a Potential Ligand for the Malarial E2 Ubiquitin-Conjugating Enzyme via Multiplexed Native Mass Spectrometry
There is an urgent need for novel therapeutics to combat <i>Plasmodium falciparum</i>, especially in light of increasing drug resistance. Here, we present a multiplexed native mass spectrometry (MS) platform capable of simultaneously screening multiple protein targets against chemically...
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MDPI AG
2025-05-01
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| Series: | Chemosensors |
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| Online Access: | https://www.mdpi.com/2227-9040/13/5/166 |
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| author | Jianying Han Wesley C. Van Voorhis Ronald J. Quinn Miaomiao Liu |
| author_facet | Jianying Han Wesley C. Van Voorhis Ronald J. Quinn Miaomiao Liu |
| author_sort | Jianying Han |
| collection | DOAJ |
| description | There is an urgent need for novel therapeutics to combat <i>Plasmodium falciparum</i>, especially in light of increasing drug resistance. Here, we present a multiplexed native mass spectrometry (MS) platform capable of simultaneously screening multiple protein targets against chemically diverse crude extracts with minimal sample preparation. A mixture of seven malarial proteins was analyzed under optimized native MS conditions, enabling the detection of specific ligand binding events. Using this platform, lithospermate B from <i>Salvia miltiorrhiza</i> (Danshen) was identified as a novel ligand for a malarial ubiquitin-conjugating enzyme with moderate affinity (Kd = 30.5 ± 2.5 μM). This is the first report linking lithospermate B to a malarial protein target, highlighting the potential of native MS to uncover new bioactivities of known natural products. This approach significantly enhances the throughput of protein–ligand screening and offers a powerful tool for early-stage natural product-based drug discovery. |
| format | Article |
| id | doaj-art-fe79cce4897b4d489cec383d275ff1d9 |
| institution | DOAJ |
| issn | 2227-9040 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| series | Chemosensors |
| spelling | doaj-art-fe79cce4897b4d489cec383d275ff1d92025-08-20T03:14:32ZengMDPI AGChemosensors2227-90402025-05-0113516610.3390/chemosensors13050166Discovery of Lithospermate B as a Potential Ligand for the Malarial E2 Ubiquitin-Conjugating Enzyme via Multiplexed Native Mass SpectrometryJianying Han0Wesley C. Van Voorhis1Ronald J. Quinn2Miaomiao Liu3Institute for Biomedicine and Glycomics, Griffith University, Brisbane, QLD 4111, AustraliaCenter for Emerging and Re-emerging Infectious Diseases, Department of Medicine, University of Washington School of Medicine, MS 358061, 750 Republican St., Seattle, WA 98109-4766, USAInstitute for Biomedicine and Glycomics, Griffith University, Brisbane, QLD 4111, AustraliaInstitute for Biomedicine and Glycomics, Griffith University, Brisbane, QLD 4111, AustraliaThere is an urgent need for novel therapeutics to combat <i>Plasmodium falciparum</i>, especially in light of increasing drug resistance. Here, we present a multiplexed native mass spectrometry (MS) platform capable of simultaneously screening multiple protein targets against chemically diverse crude extracts with minimal sample preparation. A mixture of seven malarial proteins was analyzed under optimized native MS conditions, enabling the detection of specific ligand binding events. Using this platform, lithospermate B from <i>Salvia miltiorrhiza</i> (Danshen) was identified as a novel ligand for a malarial ubiquitin-conjugating enzyme with moderate affinity (Kd = 30.5 ± 2.5 μM). This is the first report linking lithospermate B to a malarial protein target, highlighting the potential of native MS to uncover new bioactivities of known natural products. This approach significantly enhances the throughput of protein–ligand screening and offers a powerful tool for early-stage natural product-based drug discovery.https://www.mdpi.com/2227-9040/13/5/166native mass spectrometrylithospermate Bubiquitin-conjugating enzyme<i>Salvia miltiorrhiza</i> |
| spellingShingle | Jianying Han Wesley C. Van Voorhis Ronald J. Quinn Miaomiao Liu Discovery of Lithospermate B as a Potential Ligand for the Malarial E2 Ubiquitin-Conjugating Enzyme via Multiplexed Native Mass Spectrometry Chemosensors native mass spectrometry lithospermate B ubiquitin-conjugating enzyme <i>Salvia miltiorrhiza</i> |
| title | Discovery of Lithospermate B as a Potential Ligand for the Malarial E2 Ubiquitin-Conjugating Enzyme via Multiplexed Native Mass Spectrometry |
| title_full | Discovery of Lithospermate B as a Potential Ligand for the Malarial E2 Ubiquitin-Conjugating Enzyme via Multiplexed Native Mass Spectrometry |
| title_fullStr | Discovery of Lithospermate B as a Potential Ligand for the Malarial E2 Ubiquitin-Conjugating Enzyme via Multiplexed Native Mass Spectrometry |
| title_full_unstemmed | Discovery of Lithospermate B as a Potential Ligand for the Malarial E2 Ubiquitin-Conjugating Enzyme via Multiplexed Native Mass Spectrometry |
| title_short | Discovery of Lithospermate B as a Potential Ligand for the Malarial E2 Ubiquitin-Conjugating Enzyme via Multiplexed Native Mass Spectrometry |
| title_sort | discovery of lithospermate b as a potential ligand for the malarial e2 ubiquitin conjugating enzyme via multiplexed native mass spectrometry |
| topic | native mass spectrometry lithospermate B ubiquitin-conjugating enzyme <i>Salvia miltiorrhiza</i> |
| url | https://www.mdpi.com/2227-9040/13/5/166 |
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