Ac4GlcNAcF3, an OGT-tolerated but OGA-resistant regulator for O-GlcNAcylation.
Bioorg Med Chem Lett
; 29(6): 802-805, 2019 03 15.
Article
em En
| MEDLINE
| ID: mdl-30713024
ABSTRACT
O-Linked N-acetylglucosamine (O-GlcNAc) is an abundant posttranslationalmonosaccaride-modification found on Ser or Thr residues of intracellular proteins in most eukaryotes. The dynamic nature of O-GlcNAc has enabled researchers to modulate the stoichiometry of O-GlcNAc on proteins in order to investigate its function. Cell permeable small moleculars have proven invaluable tools to increase O-GlcNAc levels. Herein, using in vitro substrate screening, we identified GlcNAcF3 as an OGT-accepted but OGA-resistant sugar mimic. Cellular experiments with cell-permeable peracetylated-GlcNAcF3 (Ac4GlcNAcF3) displayed that Ac4GlcNAcF3 was a potent tool to increase O-GlcNAc levels in several cell lines. Further, NIH3T3 cells interfered with OGT (siOGT) showed significant decreasing of O-GlcNAc levels with Ac4GlcNAcF3 treatment, indicating O-GlcNAcF3 was an OGT-dependent modification. In addition, cellular toxic assay confirmed O-GlcNAcF3 production has no significant effect on cell proliferation or viability. Thus, Ac4GlcNAcF3 represents a safe and dual regulator for both OGT and OGA, which will benefit the study of O-GlcNAc.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Acetilglucosamina
/
Beta-N-Acetil-Hexosaminidases
/
N-Acetilglucosaminiltransferases
/
Inibidores Enzimáticos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China