Chemoproteomics for Plasmodium Parasite Drug Target Discovery.

Journal Article (Review;Journal Article)

Emerging Plasmodium parasite drug resistance is threatening progress towards malaria control and elimination. While recent efforts in cell-based, high-throughput drug screening have produced first-in-class drugs with promising activities against different Plasmodium life cycle stages, most of these antimalarial agents have elusive mechanisms of action. Though challenging to address, target identification can provide valuable information to facilitate lead optimization and preclinical drug prioritization. Recently, proteome-wide methods for direct assessment of drug-protein interactions have emerged as powerful tools in a number of systems, including Plasmodium. In this review, we will discuss current chemoproteomic strategies that have been adapted to antimalarial drug target discovery, including affinity- and activity-based protein profiling and the energetics-based techniques thermal proteome profiling and stability of proteins from rates of oxidation. The successful application of chemoproteomics to the Plasmodium blood stage highlights the potential of these methods to link inhibitors to their molecular targets in more elusive Plasmodium life stages and intracellular pathogens in the future.

Full Text

Duke Authors

Cited Authors

  • Lu, K-Y; Mansfield, CR; Fitzgerald, MC; Derbyshire, ER

Published Date

  • August 2021

Published In

Volume / Issue

  • 22 / 16

Start / End Page

  • 2591 - 2599

PubMed ID

  • 33999499

Pubmed Central ID

  • PMC8373781

Electronic International Standard Serial Number (EISSN)

  • 1439-7633

International Standard Serial Number (ISSN)

  • 1439-4227

Digital Object Identifier (DOI)

  • 10.1002/cbic.202100155

Language

  • eng