20.500.12556/RUL-133856 Intracellular hydrolysis of small-molecule O-linked N-acetylglucosamine transferase inhibitors differs among cells and is not required for its inhibition 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. ester hydrolysis inhibitor O-GlcNAc transferase OGT inhibitor terapevtska uporaba metaboliti true false true Angleški jezik Slovenski jezik Članek v reviji 2021-12-17 10:22:58 2021-12-17 10:23:02 2023-03-27 07:34:24 0000-00-00 00:00:00 2020 0 0 10 str. iss. 15, art. 3381 Vol. 25 2020 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 577.121:615 1420-3049 10.3390/molecules25153381 24851459 RAZ_Loi_Elena_Maria_2020.pdf RAZ_Loi_Elena_Maria_2020.pdf 1 F9FAB238294F772015A8EC75E1291F30 b5cabae44ea51d2d21af6434c3129d03887e84bd35f0faf147ef91ddf3ac7742 0b92df34-5f1b-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=152211 https://www.mdpi.com/1420-3049/25/15/3381 0 cdd75a63-5f1a-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=152210 Fakulteta za farmacijo 0 0 0