Back to Search
Start Over
Intracellular Hydrolysis of Small-Molecule O-Linked N-Acetylglucosamine Transferase Inhibitors Differs among Cells and Is Not Required for Its Inhibition
- Source :
- Molecules (Basel, Switzerland), 25(15). Multidisciplinary Digital Publishing Institute (MDPI), Molecules, vol. 25, no. 15, 3381, 2020., Molecules, Volume 25, Issue 15, Molecules, 10 str. : Ilustr., Vol. 25, iss. 15, art. 3381, 2020, COBISS-ID: 18462981, Molecules, Vol 25, Iss 3381, p 3381 (2020)
- Publication Year :
- 2020
-
Abstract
- 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. Nasl. z nasl. zaslona. Opis vira z dne 11. 8. 2020. Št. članka: 3381. Abstract. Bibliografija: str. 9-10. European Union’s Horizon2020 program under the Marie Skłodowska-Curie, PhD4GlycoDrug COST actions, Innogly COST Actions, GLYCONanoPROBES
- Subjects :
- metaboliti
ester hydrolysis, inhibitor, O-GlcNAc transferase, OGT inhibitor
ester hydrolysis
Pharmaceutical Science
010402 general chemistry
01 natural sciences
Analytical Chemistry
lcsh:QD241-441
03 medical and health sciences
lcsh:Organic chemistry
Drug Discovery
Transferase
Moiety
Physical and Theoretical Chemistry
Metaboliti
030304 developmental biology
chemistry.chemical_classification
inhibitor
O-GlcNAc transferase
OGT inhibitor
0303 health sciences
Chemistry
Organic Chemistry
udc:615
Small molecule
0104 chemical sciences
Enzyme
Biochemistry
Cytoplasm
Cell culture
Chemistry (miscellaneous)
terapevtska uporaba
Molecular Medicine
Terapevtska uporaba
udc:577.121:615
Function (biology)
Intracellular
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Database :
- OpenAIRE
- Journal :
- Molecules (Basel, Switzerland), 25(15). Multidisciplinary Digital Publishing Institute (MDPI), Molecules, vol. 25, no. 15, 3381, 2020., Molecules, Volume 25, Issue 15, Molecules, 10 str. : Ilustr., Vol. 25, iss. 15, art. 3381, 2020, COBISS-ID: 18462981, Molecules, Vol 25, Iss 3381, p 3381 (2020)
- Accession number :
- edsair.doi.dedup.....f42ae4644399e4e3484cf066ad9c0ee3