Identification of antimalarial targets of chloroquine by a combined deconvolution strategy of ABPP and MS-CETSA.

ABSTRACT:

Background

Malaria is a devastating infectious disease that disproportionally threatens hundreds of millions of people in developing countries. In the history of anti-malaria campaign, chloroquine (CQ) has played an indispensable role, however, its mechanism of action (MoA) is not fully understood.

Methods

We used the principle of photo-affinity labeling and click chemistry-based functionalization in the design of a CQ probe and developed a combined deconvolution strategy of activity-based protein profiling (ABPP) and mass spectrometry-coupled cellular thermal shift assay (MS-CETSA) that identified the protein targets of CQ in an unbiased manner in this study. The interactions between CQ and these identified potential protein hits were confirmed by biophysical and enzymatic

SUBMITTER: Gao P 

PROVIDER: S-EPMC9195458 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature