title: Systematic synthesis and inhibitory activity of haloacetamidyl oligosaccharide derivatives toward cytoplasmic peptide:N-glycanase.
abstract: 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, beta-chloropropionamidyl chitobiose, and chloroacetamidyl cellooligosaccharide derivatives did not show any activity. These results underscore the importance of the N-acetyl groups of chitobiose for PNGase recognition. In addition, reactivity and position of the leaving group at the reducing end are also important factors.
authors.affiliation: The Institute of Physical and Chemical Research, Wako, Saitama, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Miyazaki
authors.forename: Ichiro
authors.initials: I
authors.lastname: Matsuo
authors.forename: Shinya
authors.initials: S
authors.lastname: Hagihara
authors.forename: Ayako
authors.initials: A
authors.lastname: Kakegawa
authors.forename: Tadashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yukishige
authors.initials: Y
authors.lastname: Ito
mesh_terms: D000081:Acetamides / Q000737:chemistry*; D003593:Cytoplasm / Q000201:enzymology* / Q000378:metabolism; D004187:Disaccharides / Q000138:chemical synthesis / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D008958:Models, Molecular; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000494:pharmacology*; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010455:Peptides
chemical_list: D000081:Acetamides; D004187:Disaccharides; D004791:Enzyme Inhibitors; D009844:Oligosaccharides; D010455:Peptides; C032438:chitobiose; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase