Systematic synthesis and inhibitory activity of haloacetamidyl oligosaccharide derivatives toward cytoplasmic peptide:N-glycanase.
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.
Miyazaki
Ayako
A
The Institute of Physical and Chemical Research, Wako, Saitama, Japan.
Matsuo
Ichiro
I
Hagihara
Shinya
S
Kakegawa
Ayako
A
Suzuki
Tadashi
T
Ito
Yukishige
Y
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
D000081:Acetamides; D004187:Disaccharides; D004791:Enzyme Inhibitors; D009844:Oligosaccharides; D010455:Peptides; C032438:chitobiose; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase