Description
Proteins can be modified post-translationally by the addition of
O-linked N-acetylglucosamine (
O-GlcNAc). Nuclear cytoplasmic
O-GlcNAcase and acetyltransferase (NCOAT) is a β-N-acetylglucosaminidase that removes GlcNAc from
O-glycosylated proteins. PUGNAc is a (phenylcarbamoyl)oxime analog of GlcNAc that reversibly inhibits NCOAT (K
i = 40-110 nM). It also less potently inhibits other hexosaminidases and exochitinases. (Z)-PUGNAc is a stereoisomer of PUGNAc that is a more potent inhibitor of NCOAT than the (E) isomer, both
in vitro and in cells.
Chemical Properties
White to Off-White Solid
Uses
An inhibitor of O-GlcNAcase, hexosaminidase A, and hexosaminidase B
Uses
O-(2-acetamido-2deoxy-D-glucopyranosylidene)amino-
N-phenylcarbamate (PUGNAc) has been used to evaluate the effects of silibinin on
O-GlcNAc levels of glycoproteins in Adult Retinal Pigment Epithelial-19 (ARPE-19) cells. It has also been used as a component of the HEPES lysis buffer for rat brain samples.
Biological Activity
O -GlcNAc- β - N -acetylglucosaminidase ( O -GlcNAcase) and β -hexosaminidase inhibitor (K i values are 46 and 36 nM respectively) that increases O -GlcNAc levels ~ 2-fold in HT29 cells. Z -linked isomer is more potent than the E isomer.
Biochem/physiol Actions
O-(2-acetamido-2deoxy-D-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc) induces insulin resistance in 3T3-L1 adipocytes by reducing insulin-prompting phosphorylation of protein kinase B (Akt) and glycogen synthase kinase 3β (GSK3β).
storage
Desiccate at -20°C
References
[1] MATTHEW S MACAULEY. O-GlcNAcase uses substrate-assisted catalysis: kinetic analysis and development of highly selective mechanism-inspired inhibitors.[J]. The Journal of Biological Chemistry, 2005, 280 27: 25313-25322. DOI:
10.1074/jbc.m413819200[2] ZACHARY T KNEASS Richard B M. Protein O-GlcNAc modulates motility-associated signaling intermediates in neutrophils.[J]. The Journal of Biological Chemistry, 2005: 14579-14585. DOI:
10.1074/jbc.m414066200[3] LUYUN ZOU. The protective effects of PUGNAc on cardiac function after trauma-hemorrhage are mediated via increased protein O-GlcNAc levels.[J]. SHOCK, 2007, 27 4: 402-408. DOI:
10.1097/01.shk.0000245031.31859.29[4] EDWARD B ARIAS Gregory D C Junghoon Kim. Prolonged incubation in PUGNAc results in increased protein O-Linked glycosylation and insulin resistance in rat skeletal muscle.[J]. Diabetes, 2004, 53 4: 921-930. DOI:
10.2337/diabetes.53.4.921
