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Intracellular hydrolysis of small-molecule O-linked N-acetylglucosamine transferase inhibitors differs among cells and is not required for its inhibition [Elektronski vir]Loi, Elena Maria ...O-GlcNAcylation is an essential post-translational modification that occurs on nuclear and cytoplasmic proteins, regulating their function in response to cellular stress and altered nutrient ... availability. O-GlcNAc transferase (OGT) is the enzyme that catalyzes this reaction and represents a potential therapeutic target, whose biological role is still not fully understood. To support this research field, a series of cell-permeable, low-nanomolar OGT inhibitors were recently reported. In this study, we resynthesized the most potent OGT inhibitor of the library, OSMI-4, and we used it to investigate OGT inhibition in different human cell lines. The compound features an ethyl ester moiety that is supposed to be cleaved by carboxylesterases to generate its active metabolite. Our LC-HRMS analysis of the cell lysates shows that this is not always the case and that, even in the cell lines where hydrolysis does not occur, OGT activity is inhibited.Source: Molecules [Elektronski vir]. - ISSN 1420-3049 (Vol. 25, iss. 15, art. 3381, 2020, 10 str.)Type of material - e-article ; adult, seriousPublish date - 2020Language - englishCOBISS.SI-ID - 24851459
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https://www.mdpi.com/1420-3049/25/15/3381Prost dostop
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Author | Loi, Elena Maria ... |
Title | Intracellular hydrolysis of small-molecule O-linked N-acetylglucosamine transferase inhibitors differs among cells and is not required for its inhibition [Elektronski vir] |
Publication date | 2020-07-25 |
COBISS.SI-ID | 24851459 |
Publication version in repository | Publisher's version |
Publication licence | Creative Commons Attribution 4.0 International |
Embargo | Immediate publication for public |
Project(s) from which the publication was funded
Title | Acronym | Project ID | Funder |
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Multidisciplinary European Joint Doctorate in the Design and Development of Glyco Drugs | PhD4GlycoDrug | 765581 |
European Commission |
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Loi, Elena Maria | ![]() |
Weiss, Matjaž | 50503 |
Pajk, Stane, 1983- | 28861 |
Gobec, Martina, 1983- | 32034 |
Tomašič, Tihomir | 28334 |
Pieters, Roland J. | ![]() |
Anderluh, Marko | 21456 |
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