Miyazaki Ayako, Matsuo Ichiro, Hagihara Shinya, Kakegawa Ayako, Suzuki Tadashi, Ito Yukishige
The Institute of Physical and Chemical Research, Wako, Saitama, Japan.
Glycoconj J. 2009 Feb;26(2):133-40. doi: 10.1007/s10719-008-9171-3. Epub 2008 Aug 10.
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.
合成了一系列糖基卤代乙酰胺，作为细胞质肽：N-聚糖酶（PNGase）的潜在抑制剂，该酶可从错误折叠的糖蛋白中去除N-聚糖。氯代、溴代和碘代乙酰氨基壳二糖及壳四糖衍生物表现出显著的抑制活性。氟代乙酰氨基衍生物未观察到抑制活性。此外，N-乙酰葡糖胺衍生物、β-氯丙酰氨基壳二糖和氯乙酰氨基纤维寡糖衍生物均未显示任何活性。这些结果强调了壳二糖的N-乙酰基对PNGase识别的重要性。此外，还原端离去基团的反应性和位置也是重要因素。
