Elena Maria Loi (Avtor), Matjaž Weiss (Avtor), Stane Pajk (Avtor), Martina Gobec (Avtor), Tihomir Tomašić (Avtor), Roland J. Pieters (Avtor), Marko Anderluh (Avtor)

Povzetek

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.

Ključne besede

ester hydrolysis;inhibitor;O-GlcNAc transferase;OGT inhibitor;

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: UL FFA - Fakulteta za farmacijo
UDK: 577.121:615
COBISS: 24851459 Povezava se bo odprla v novem oknu
ISSN: 1420-3049
Št. ogledov: 255
Št. prenosov: 107
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarni jezik: Slovenski jezik
Sekundarne ključne besede: Terapevtska uporaba;Metaboliti;
Vrsta dela (COBISS): Članek v reviji
Strani: 10 str.
Letnik: ǂVol. ǂ25
Zvezek: ǂiss. ǂ15, ǂart. ǂ3381
Čas izdaje: 2020
DOI: 10.3390/molecules25153381
ID: 14110134