多様なマンノシダーゼを区別するための糖タンパク質プロセッシング阻害剤の利用法

DOI 被引用文献1件
  • Kaushal G. P.
    Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences
  • Elbein A. D.
    Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences
  • 鈴木 慈郎
    豊橋技術大学・物質工学
  • 西村 吉雄
    微生物化学研究所

書誌事項

タイトル別名
  • The Use of Glycoprotein Processing Inhibitors to Distinguish Various Mannosidases.

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説明

A number of compounds have been identified over the past 10 years that inhibit specific glycosidases involved in the processing of N-linked oligosaccharides. These compounds include specific α-glucosidase and α-mannosidase inhibitors that block removal of either glucose or mannose residues at specific steps in the processing pathway, and cause the formation of altered carbohydrate structures. Many of these inhibitors have been widely used in cell culture to assess the role of specific oligosaccharide chains in the function of a given glycoprotein. In addition, these inhibitors have been useful tools to distinguish various glycosidases, as well as for producing affinity ligands for the purification of specific glycosidases. In particular, there are now several potent and selective inhibitors that show such activities towards the various α-mannosidases. With these inhibitors, a clear distinction can be made between the processing α-1, 2 specific mannosidases (i.e., mannosidase I), mannosidase II that cleaves both α1, 3 and α1, 6 linked mannoses from the GlcNAcMan5 (GlcNAc)2 substrate, and the broad-specificity α-mannosidases that release all of the α1, 2-, α1, 3- and α1, 6-linked mannoses from an9-4(GlcNAc)2 structures. Thus, deoxymannojirimycin or kifunensine strongly inhibit the Golgi mannosidase I, but have no effect on the Golgi mannosidase II, aryl or lysosomal α-mannosidases, and broad-specificity mannosidases. On the other hand, swainsonine and mannostatin A strongly inhibit mannosidase II, but are inactive on mannosidase I or the ER α-mannosidase. In addition, a new inhibitor, D-mannonolactam amidrazone, is a general mannosidase inhibitor that has been synthesized chemically, and this compound should provide new insight into the design of other useful and more specific inhibitors for other α-mannosidases.

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