On the utility of ultrafast MS1-only proteomics in drug target discovery studies based on thermal proteome profiling method.

Autor: Fedorov II; V. L. Talrose Institute for Energy Problems of Chemical Physics, N. N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, Leninsky Pr. 38, Bld.2, 119334, Moscow, Russia.; Moscow Center for Advanced Studies, Kulakova Str. 20, 123592, Moscow, Russia., Bubis JA; V. L. Talrose Institute for Energy Problems of Chemical Physics, N. N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, Leninsky Pr. 38, Bld.2, 119334, Moscow, Russia., Kazakova EM; V. L. Talrose Institute for Energy Problems of Chemical Physics, N. N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, Leninsky Pr. 38, Bld.2, 119334, Moscow, Russia., Lobas AA; V. L. Talrose Institute for Energy Problems of Chemical Physics, N. N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, Leninsky Pr. 38, Bld.2, 119334, Moscow, Russia., Ivanov MV; V. L. Talrose Institute for Energy Problems of Chemical Physics, N. N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, Leninsky Pr. 38, Bld.2, 119334, Moscow, Russia., Emekeeva DD; V. L. Talrose Institute for Energy Problems of Chemical Physics, N. N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, Leninsky Pr. 38, Bld.2, 119334, Moscow, Russia., Tarasova IA; V. L. Talrose Institute for Energy Problems of Chemical Physics, N. N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, Leninsky Pr. 38, Bld.2, 119334, Moscow, Russia., Nazarov AA; Faculty of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1/3, 119991, Moscow, Russia.; Faculty of Chemistry of the National Research University Higher School of Economics, Vavilova Str. 7, 101000, Moscow, Russia., Gorshkov MV; V. L. Talrose Institute for Energy Problems of Chemical Physics, N. N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, Leninsky Pr. 38, Bld.2, 119334, Moscow, Russia. mike.gorshkov@gmail.com.
Jazyk: angličtina
Zdroj: Analytical and bioanalytical chemistry [Anal Bioanal Chem] 2024 Jul; Vol. 416 (18), pp. 4083-4089. Date of Electronic Publication: 2024 May 15.
DOI: 10.1007/s00216-024-05330-9
Abstrakt: Advances in high-throughput high-resolution mass spectrometry and the development of thermal proteome profiling approach (TPP) have made it possible to accelerate a drug target search. Since its introduction in 2014, TPP quickly became a method of choice in chemical proteomics for identifying drug-to-protein interactions on a proteome-wide scale and mapping the pathways of these interactions, thus further elucidating the unknown mechanisms of action of a drug under study. However, the current TPP implementations based on tandem mass spectrometry (MS/MS), associated with employing lengthy peptide separation protocols and expensive labeling techniques for sample multiplexing, limit the scaling of this approach for the ever growing variety of drug-to-proteomes. A variety of ultrafast proteomics methods have been developed in the last couple of years. Among them, DirectMS1 provides MS/MS-free quantitative proteome-wide analysis in 5-min time scale, thus opening the way for sample-hungry applications, such as TPP. In this work, we demonstrate the first implementation of the TPP approach using the ultrafast proteome-wide analysis based on DirectMS1. Using a drug topotecan, which is a known topoisomerase I (TOP1) inhibitor, the feasibility of the method for identifying drug targets at the whole proteome level was demonstrated for an ovarian cancer cell line.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)
Databáze: MEDLINE
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