Multiplexed Proteome Profiling of Targeted Protein Degradation With Data-Independent Acquisition-Based Mass Spectrometry

ABSTRACT: Targeted protein degradation (TPD) has become a powerful and promising tool that can effective trigger the degradation of specific disease-related proteins utilizing the endogenous pathways of the organism. However, the global proteomic profiling of TPD with multiple dimensions remains lacking since traditional methods of protein quantification are low-throughput and time-consuming. Mass spectrometry (MS)-based quantitative proteomics have been used in TPD research. The quantification with isobaric mass tagging has the problems such as preference for high-abundance species, high cost and ratio compression effects. Here, we employed data-independent acquisition (DIA) MS with multiplexed proteome profiling of TPD, termed DIA-MPT, to implement the label-free proteomic quantitation with satisfactory reproducibility and high accuracy. We demonstrated the power of DIA-MPT for comprehensive profiling of proteolysis targeting chimera (PROTAC) degraders of bromodomain and extra-terminal (BET) and signal transducer and activator of transcription 3 (STAT3) with pharmacodynamic response and drug sensitivity analysis. Consequently, DIA-MPT has potential as a new platform for high-throughput, flexible, and comprehensive multidimensional proteomic profiling of TPD.

ORGANISM(S): Homo Sapiens Mus Musculus

SUBMITTER: Hu Zhou  

PROVIDER: PXD050426 | iProX | Wed Mar 06 00:00:00 GMT 2024

REPOSITORIES: iProX