Studying Target-Engagement of Anti-Infectives by Solvent-Induced Protein Precipitation and Quantitative Mass Spectrometry.

ABSTRACT: Antimicrobial resistance (AMR) poses a serious threat to global health. The rapid emergence of resistance contrasts with the slow pace of antimicrobial development, emphasizing the urgent need for innovative drug discovery approaches. This study addresses a critical bottleneck in early drug development by introducing integral solvent-induced protein precipitation (iSPP) to rapidly assess the target-engagement of lead compounds in extracts of pathogenic microorganisms under close-to-physiological conditions. iSPP measures the change in protein stability against solvent-induced precipitation in the presence of ligands. The iSPP method for bacteria builds upon established SPP procedures and features optimized denaturation gradients and minimized sample input amounts. The effectiveness of the

SUBMITTER: Bizzarri L 

PROVIDER: S-EPMC11650766 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature