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REVIEW: Mass Spectrometry-Based Chemical Proteomics for Drug Target Discoveries

Ivan I. Fedorov1,2, Victoria I. Lineva2, Irina A. Tarasova1, and Mikhail V. Gorshkov1,a*

1V. L. Talrose Institute for Energy Problems of Chemical Physics, N. N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, 119334 Moscow, Russia

2Moscow Institute of Physics and Technology (National University), 141700 Dolgoprudny, Moscow Region, Russia

* To whom correspondence should be addressed.

Received May 27, 2022; Revised July 4, 2022; Accepted July 6, 2022
Chemical proteomics, emerging rapidly in recent years, has become a main approach to identifying interactions between the small molecules and proteins in the cells on a proteome scale and mapping the signaling and/or metabolic pathways activated and regulated by these interactions. The methods of chemical proteomics allow not only identifying proteins targeted by drugs, characterizing their toxicity and discovering possible off-target proteins, but also elucidation of the fundamental mechanisms of cell functioning under conditions of drug exposure or due to the changes in physiological state of the organism itself. Solving these problems is essential for both basic research in biology and clinical practice, including approaches to early diagnosis of various forms of serious diseases or prediction of the effectiveness of therapeutic treatment. At the same time, recent developments in high-resolution mass spectrometry have provided the technology for searching the drug targets across the whole cell proteomes. This review provides a concise description of the main objectives and problems of mass spectrometry-based chemical proteomics, the methods and approaches to their solution, and examples of implementation of these methods in biomedical research.
KEY WORDS: chemical proteomics, mass-spectrometry, drug targets

DOI: 10.1134/S0006297922090103