Work

Discovery of Lithospermate B as a Potential Ligand for the Malarial E2 Ubiquitin-Conjugating Enzyme via Multiplexed Native Mass Spectrometry

Year: 2025

Type: article

Abstract: There is an urgent need for novel therapeutics to combat Plasmodium falciparum, 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 Salvia miltiorrhiza (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.

Source: Chemosensors

DOI: 10.3390/chemosensors13050166

Authors: Jianying Han, Wesley C. Van Voorhis, Ronald J. Quinn, Miaomiao Liu

Institutions: Griffith University, The University of Queensland, Institute for Molecular Bioscience, University of Washington

Language: English

Topic: Mass Spectrometry Techniques and Applications

Subfield: Spectroscopy

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,413