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...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-05-01
|
| Series: | Chemosensors |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9040/13/5/166 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | 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. |
|---|---|
| ISSN: | 2227-9040 |