聚合物负载及化学酶法合成脑膜炎奈瑟菌五糖：方法学比较

Polymer-supported and chemoenzymatic synthesis of the Neisseria meningitidis pentasaccharide: a methodological comparison.

作者信息

Yan F, Wakarchuk W W, Gilbert M, Richards J C, Whitfield D M

机构信息

Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ont.

出版信息

Carbohydr Res. 2000 Aug 18;328(1):3-16. doi: 10.1016/s0008-6215(00)00086-0.

DOI:10.1016/s0008-6215(00)00086-0

PMID:11005572

Abstract

Neisseria meningitidis trisaccharide [GlcNAc[(1-->3)Galbeta(1-->4)Glc-R], tetrasaccharide [Galbeta(1-->4)GlcNAcbeta(1--> 3)Galbeta(1-->4)Glc-R], and a pentasaccharide [Neu5Acalpha(2-->3)Galbeta(1-->4)GlcNAcbeta(1-->3)G albeta(1-->4)Glc-SPh] were prepared via conventional chemical synthesis, polymer-supported synthesis, and chemoenzymatic methods, starting from D-lactose. The polymer polyethyleneglycol monomethylether (MPEG) and the linker dioxyxylene (DOX) were used with a lactose-bound acceptor to improve the purification process. Several enzymes (LgtA, GalE-LgtB fusion, and CMP-Neu5Ac synthetase/sialyltransferase fusion) were used for syntheses of these oligosaccharides. Excellent stereo- and regioselectivities as well as high yield (> 90% from Gal(1-->4)Glc-SPh) of the pentasaccharide were obtained. Both of the convenient processes are suitable for efficient preparation of target oligosaccharides.

摘要

脑膜炎奈瑟菌三糖[GlcNAc[(1→3)Galβ(1→4)Glc-R]、四糖[Galβ(1→4)GlcNAcβ(1→3)Galβ(1→4)Glc-R]和五糖[Neu5Acα(2→3)Galβ(1→4)GlcNAcβ(1→3)Galβ(1→4)Glc-SPh]通过传统化学合成、聚合物支持合成和化学酶法，以D-乳糖为起始原料制备。聚合物聚乙二醇单甲醚（MPEG）和连接体二氧杂环戊烯（DOX）与乳糖结合的受体一起使用，以改进纯化过程。几种酶（LgtA、GalE-LgtB融合蛋白和CMP-Neu5Ac合成酶/唾液酸转移酶融合蛋白）用于这些寡糖的合成。获得了优异的立体和区域选择性以及五糖的高产率（从Gal(1→4)Glc-SPh得到>90%）。这两种简便方法都适合于高效制备目标寡糖。