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

  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},
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… 

Synthesis of a Versatile Probe for Analysis of Cytoplasmic Peptide-N-Glycanase

A clickable alkyne tagged chloroacetamidyl chitobiose derivative was synthesized as a potential inhibitor of cytoplasmic peptide-N-glycanase and obtained the fluorescent labeled disaccharide derivative, selectively, selectively.

Irreversible inhibitors and activity-based probes as research tools in chemical glycobiology.

In this review, we will discuss the enzymes that are involved in the synthesis and degradation of glycoconjugates and we will give an overview of the inhibitors and activity-based probes (ABPs) that

Mechanism-based inhibition of GH127/146 cysteine glycosidases by stereospecifically functionalized l-arabinofuranosides.

Additional examinations using l-Araf-azides resulted in further mechanistic observations of the GH127/146 cysteine glycosidases, including the hydrolysis of β-5 as the substrate and oxidative inhibition by α-5 using the GH 127 homologue.

The Neurospora Peptide:N-Glycanase Ortholog PNG1 Is Essential for Cell Polarity despite Its Lack of Enzymatic Activity*

It is shown that the PNG1 ortholog from the filamentous ascomycete Neurospora crassa is an essential protein, and its deletion results in strong polarity defects and so far unrecognized enzyme-independent function of PNG1 that may only become apparent in highly polar cells such as fungal hyphae.

My Stroll in the Backyard of Carbohydrate Chemistry

The fields of “Glycobiology” and “Glycotechnology” are gaining an increasing amount of attention. A major part of my research has been directed at the synthesis and functional analysis of

Study on 1,3,5-triazine chemistry in dehydrocondensation: gauche effect on the generation of active triazinylammonium species.

The theory of "gauche β-alkyl group effect" proposed here provides useful guidelines for the preparation of DMT-Ams possessing various tertiary amine moieties, including trimethylamine and quinuclidine without such alkyl groups readily react with CDMT whereas triethyamine, possessing two or three such gauche β -alkyl groups in the stable conformations, does not react at all.

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2009–2010

  • D. Harvey
  • Chemistry
    Mass spectrometry reviews
  • 2015
This review is the sixth update of the original article published in 1999 on the application of MALDI mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the

Evidence for an Essential Deglycosylation-Independent Activity of PNGase in Drosophila melanogaster

Pngl was shown to be inevitable for the proper developmental transition and the biochemical properties other than deglycosylation activity is important for its biological function.

ERADication of EDEM1 occurs by selective autophagy and requires deglycosylation by cytoplasmic peptide N-glycanase

It is shown that ER degradation-enhancing α-mannosidase-like 1 protein EDEM1 is degraded by selective autophagy, providing novel insight into the mechanism of autophagic degradation of the ER-associated protein degradation (ERAD) component and disclosing hitherto unknown parallels with the clearance of cytoplasmic aggregates of misfolded proteins by selective Autophagy.



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.

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.