title: Synthesis and biological evaluation of a chitobiose-based peptide N-glycanase inhibitor library.
abstract: Peptide N-glycanase (PNGase), the enzyme responsible for the deglycosylation of N-linked glycoproteins, has an active site related to that of cysteine proteases. Chitiobiose was equipped with electrophilic traps often used in cysteine protease inhibitors, and the resulting compounds were evaluated as PNGase inhibitors. We found that the electrophilic trap of the inhibitor has a great influence on the potency of the compounds with the chloromethyl ketone inhibitor being the first potent C-glycoside-based PNGase inhibitor.
authors.affiliation: Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
authors.forename: Martin D
authors.initials: MD
authors.lastname: Witte
authors.forename: Danielle
authors.initials: D
authors.lastname: Horst
authors.forename: Emmanuel J H J
authors.initials: EJ
authors.lastname: Wiertz
authors.forename: Gijsbert A
authors.initials: GA
authors.lastname: van der Marel
authors.forename: Herman S
authors.initials: HS
authors.lastname: Overkleeft
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry; D004187:Disaccharides / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / Q000037:antagonists & inhibitors*; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013379:Substrate Specificity
chemical_list: D000081:Acetamides; D015853:Cysteine Proteinase Inhibitors; D004187:Disaccharides; D004791:Enzyme Inhibitors; D054852:Small Molecule Libraries; C032438:chitobiose; C030686:acetamide; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase