Ultrahigh-Throughput Liquid Chromatography with Tandem Mass Spectrometry Method for Targeted Protein Degradation Compound Screening Using the Orbitrap Astral Mass Spectrometer

Key Points

• This research aims to develop an ultrahigh-throughput liquid chromatography and tandem mass spectrometry method to screen for targeted protein degradation compounds.
• Developed an ultrahigh-throughput liquid chromatography-tandem mass spectrometry method.
• Assessed dose-dependent degradation patterns of pomalidomide, iberdomide, and mezigdomide.
• Utilized the Orbitrap Astral Mass Spectrometer for proteome analysis.
• Mezigdomide shows enhanced efficacy in T cells by degrading IKZF2 and boosting anticancer immunity.
• Achieved a quantitation accuracy of 0.999 for the yeast proteome.
• Method demonstrates excellent proteome coverage suitable for drug library screening.

Abstract