A modification-centric assessment tool for the performance of chemoproteomic probes

Autor: Ji-Xiang He, Zheng-Cong Fei, Ling Fu, Cai-Ping Tian, Fu-Chu He, Hao Chi, Jing Yang
Rok vydání: 2022
Předmět:
Zdroj: Nature Chemical Biology. 18:904-912
ISSN: 1552-4469
1552-4450
Popis: Chemoproteomics has emerged as a key technology to expand the functional space in complex proteomes for probing fundamental biology and for discovering new small-molecule-based therapies. Here we report a modification-centric computational tool termed pChem to provide a streamlined pipeline for unbiased performance assessment of chemoproteomic probes. The pipeline starts with an experimental setting for isotopically coding probe-derived modifications that can be automatically recognized by pChem, with masses accurately calculated and sites precisely localized. pChem exports on-demand reports by scoring the profiling efficiency, modification homogeneity and proteome-wide residue selectivity of a tested probe. The performance and robustness of pChem were benchmarked by applying it to eighteen bioorthogonal probes. These analyses reveal that the formation of unexpected probe-derived modifications can be driven by endogenous reactive metabolites (for example, bioactive aldehydes and glutathione). pChem is a powerful and user-friendly tool that aims to facilitate the development of probes for the ever-growing field of chemoproteomics.
Databáze: OpenAIRE
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