Systematic synthesis and inhibitory activity of haloacetamidyl oligosaccharide derivatives toward cytoplasmic peptide:N-glycanase |
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| Authors: | Ayako Miyazaki Ichiro Matsuo Shinya Hagihara Ayako Kakegawa Tadashi Suzuki Yukishige Ito |
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| Affiliation: | (1) Synthetic Cellular Chemistry Laboratory, RIKEN (The Institute of Physical and Chemical Research), 2-1 Hirosawa, Wako Saitama, 351-0198, Japan;(2) Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, Japan;(3) Department of Chemistry and Chemical Biology, Gunma University, Gunma 376-8515, Japan;(4) CREST, Japan Science and Technology Agency, Kawaguchi Saitama, 332-1102, Japan;(5) 21st COE (Center of Excellence) Program, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita Osaka, 565-0871, Japan;(6) Advanced Science Institute, Chemical Biology Department, Systems Glycobiology Research Group, RIKEN (The Institute of Physical and Chemical Research), 2-1 Hirosawa, Wako Saitama, 351-0198, Japan; |
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| 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, β-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. |
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| Keywords: | Peptide:N-glycanase Haloacetamidyl oligosaccharide Inhibitor |
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