Systematic synthesis and inhibitory activity of haloacetamidyl oligosaccharide derivatives toward cytoplasmic peptide:N-glycanase

@article{Miyazaki2009SystematicSA,
  title={Systematic synthesis and inhibitory activity of haloacetamidyl oligosaccharide derivatives toward cytoplasmic peptide:N-glycanase},
  author={Aya Miyazaki and Ichiro Matsuo and Shinya Hagihara and Ayako Kakegawa and Tadashi Suzuki and Yukishige Ito},
  journal={Glycoconjugate Journal},
  year={2009},
  volume={26},
  pages={133-140}
}
A series of glycosyl haloacetamides were synthesized as potential inhibitors of cytoplasmic peptide:N-glycanase (PNGase), an enzyme that removes N-glycans from misfolded glycoproteins. Chloro-, bromo-, and iodoacetamidyl chitobiose and chitotetraose derivatives exhibited a significant inhibitory activity. No inhibitory activity was observed with of fluoroacetamididyl derivatives. Moreover, N-acetylglucosamine derivatives, β-chloropropionamidyl chitobiose, and chloroacetamidyl… 
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References

SHOWING 1-10 OF 18 REFERENCES

Site-specific Labeling of Cytoplasmic Peptide:N-Glycanase by N,N′-Diacetylchitobiose-related Compounds*

Results suggest that cytoplasmic PNGase has a separate binding site for chitobiose and other carbohydrates, and haloacetamide derivatives can irreversibly inhibit that catalytic Cys in a highly specific manner.

A simple, sensitive in vitro assay for cytoplasmic deglycosylation by peptide: N-glycanase.

Purification and enzymatic properties of peptide:N-glycanase from C3H mouse-derived L-929 fibroblast cells. Possible widespread occurrence of post-translational remodification of proteins by N-deglycosylation.

It is proposed here that PNGase-catalyzed N-deglycosylation is a functionally important universal feature in living cells.

Cytoplasmic peptide:N‐glycanase (PNGase) in eukaryotic cells: occurrence, primary structure, and potential functions

The primary structure and potential functions of the cytoplasmic PNGases are reviewed and a mouse homologue of Png1p bound not only to the Rad23 protein, but also to various proteins related to ubiquitin and/or the proteasome through an extended amino‐terminal domain.

Roles of N-linked glycans in the endoplasmic reticulum.

From a process involved in cell wall synthesis in archaea and some bacteria, N-linked glycosylation has evolved into the most common covalent protein modification in eukaryotic cells. The sugars are…

A role for N‐glycanase in the cytosolic turnover of glycoproteins

It is shown that both the yeast PNG1 enzyme and its mammalian homolog display N‐glycanase activity towards intact glycoproteins, consistent with a role for N‐ Glycanase in cytoplasmic turnover of glycoprotein turnover.

Analysis of ER-associated glycoprotein degradation using synthetic glycopeptide probes.

High-mannose-type glycan modifications of dihydrofolate reductase using glycan-methotrexate conjugates.

Expression Patterns of α2,3-Sialyltransferases and α1,3-Fucosyltransferases Determine the Mode of Sialyl Lewis X Inhibition by Disaccharide Decoys*

Regardless of the mechanism, the disaccharides blocked the cells from forming selectin ligands and inhibited adhesion to immobilized selectins, suggesting that the glycosides might prove useful for interfering with tumor cell adhesion and metastasis.

Structure of a peptide:N-glycanase-Rad23 complex: insight into the deglycosylation for denatured glycoproteins.

Complex structures in conjunction with mutational analyses revealed that the walls of the cleft block access to the active site of yPNGase by native glycoprotein, whereas theCleft is sufficiently wide to accommodate denatured glycop protein, thus explaining the specificity of PNGase for denaturing substrates.