Proteome Integral Solubility Alteration: A High-Throughput Proteomics Assay for Target Deconvolution
Gaetani M., Sabatier P., Saei A. A., Beusch C. M., Yang Z., Lundström S. L., Zubarev R. A.
Journal of Proteome Research
Vol.18, Issue11, P. 4027-4037
Опубликовано: 2019
Тип ресурса: Статья
DOI:10.1021/acs.jproteome.9b00500
Аннотация:
Various agents, including drugs as well as nonmolecular stimuli, induce alterations in the physicochemical properties of proteins in cell lysates, living cells, and organisms. These alterations can be probed by applying a stability- and solubility-modifying factor, such as elevated temperature, to a varying degree. As a second dimension of variation, drug concentration or agent intensity/concentration can be used. Compared to standard approaches where curves are fitted to protein solubility data acquired at different temperatures and drug concentrations, Proteome Integral Solubility Alteration (PISA) assay increases the analysis throughput by 1 to 2 orders of magnitude for an unlimited number of factor variation points in such a scheme. The consumption of the compound and biological material decreases in PISA by the same factor. We envision widespread use of the PISA approach in chemical biology and drug development. © 2019 American Chemical Society.
Ключевые слова:
action mechanism; chemical biology; drug development; high throughput; mass spectrometry; protein solubility; protein stability; proteomics; tandem mass tag; target deconvolution
8 azaguanine; antineoplastic agent; bortezomib; CSK protein; dasatinib; dihydrofolate reductase; floxuridine; fluorouracil; frk protein; gefitinib; methotrexate; mitogen activated protein kinase 14; nutlin; phosphotransferase; protein tyrosine kinase; raltitrexed; thymidylate synthase; topotecan; unclassified drug; vincristine; zak protein; antimetabolite; proteinase inhibitor; proteome; A-498 cell line; A-549 cell line; ab initio calculation; Article; drug targeting; fractionation; high throughput screening; human; human cell; IC50; liquid chromatography-mass spectrometry; melting temperature; pH; priority journal; protein analysis; protein stability; proteome integral solubility alteration assay; proteomics; algorithm; chemistry; drug effect; high throughput screening; liquid chromatography; metabolism; procedures; proteomics; reproducibility; solubility; tandem mass spectrometry; temperature; tumor cell line; A549 Cells; Algorithms; Antimetabolites; Cell Line, Tumor; Chromatography,
Язык текста: Английский
ISSN: 1535-3907
Gaetani M.
Sabatier P.
Saei A. A.
Beusch C. M.
Yang Z.
Lundström S. L.
Zubarev R. A. Roman Aleksandrovich 1963-
Гаетани М.
Сабатиер П.
Саеи А. А.
Беусч C. М.
Янг З.
Лундстрöм С. Л.
Зубарев Р. А. Роман Александрович 1963-
Proteome Integral Solubility Alteration: A High-Throughput Proteomics Assay for Target Deconvolution
Текст визуальный непосредственный
Journal of Proteome Research
American Chemical Society
Vol.18, Issue11 P. 4027-4037
2019
Статья
action mechanism chemical biology drug development high throughput mass spectrometry protein solubility protein stability proteomics tandem mass tag target deconvolution
8 azaguanine antineoplastic agent bortezomib CSK protein dasatinib dihydrofolate reductase floxuridine fluorouracil frk protein gefitinib methotrexate mitogen activated protein kinase 14 nutlin phosphotransferase protein tyrosine kinase raltitrexed thymidylate synthase topotecan unclassified drug vincristine zak protein antimetabolite proteinase inhibitor proteome A-498 cell line A-549 cell line ab initio calculation Article drug targeting fractionation high throughput screening human human cell IC50 liquid chromatography-mass spectrometry melting temperature pH priority journal protein analysis protein stability proteome integral solubility alteration assay proteomics algorithm chemistry drug effect high throughput screening liquid chromatography metabolism procedures proteomics reproducibility solubility tandem mass spectrometry temperature tumor cell line A549 Cells Algorithms Antimetabolites Cell Line, Tumor Chromatography,
Various agents, including drugs as well as nonmolecular stimuli, induce alterations in the physicochemical properties of proteins in cell lysates, living cells, and organisms. These alterations can be probed by applying a stability- and solubility-modifying factor, such as elevated temperature, to a varying degree. As a second dimension of variation, drug concentration or agent intensity/concentration can be used. Compared to standard approaches where curves are fitted to protein solubility data acquired at different temperatures and drug concentrations, Proteome Integral Solubility Alteration (PISA) assay increases the analysis throughput by 1 to 2 orders of magnitude for an unlimited number of factor variation points in such a scheme. The consumption of the compound and biological material decreases in PISA by the same factor. We envision widespread use of the PISA approach in chemical biology and drug development. © 2019 American Chemical Society.