修饰的D-甘露糖核心衍生物的合成及其对GH38 α-甘露糖苷酶的影响。

Synthesis of modified D-mannose core derivatives and their impact on GH38 α-mannosidases.

作者信息

Poláková Monika, Horák Radim, Šesták Sergej, Holková Ivana

机构信息

Institute of Chemistry, Center for Glycomics, Slovak Academy of Sciences, Dúbravska cesta 9, SK-845 38 Bratislava, Slovakia.

Department of Organic Chemistry, University of Palacky, Tr.17. listopadu 12, CZ-771 46 Olomouc, Czech Republic.

出版信息

Carbohydr Res. 2016 Jun 16;428:62-71. doi: 10.1016/j.carres.2016.04.004. Epub 2016 Apr 11.

DOI:10.1016/j.carres.2016.04.004

PMID:27152630

Abstract

Nine new compounds having five- and modified six-member carbohydrate core derived from D-lyxose or D-mannose, and non-hydrolysable aglycones (benzylsulfonyl or aryl(alkyl)triazolyl) were synthesised to investigate their ability to inhibit the recombinant Drosophila melanogaster homologs of two human GH38 family enzymes: Golgi mannosidase II (dGMIIb) and lysosomal mannosidase (dLMII). Two compounds were weak selective dGMIIb inhibitors showing IC50 at mM level. Moreover, it was found that another GH38 enzyme, commercial jack bean α-mannosidase, was inhibited by triazole conjugates regardless of the carbohydrate core while the corresponding sulfones were inactive.

摘要

合成了九种新化合物，其具有源自D-来苏糖或D-甘露糖的五元及修饰的六元碳水化合物核心，以及不可水解的苷元（苄基磺酰基或芳基（烷基）三唑基），以研究它们抑制两种人类GH38家族酶的重组果蝇同源物的能力：高尔基体甘露糖苷酶II（dGMIIb）和溶酶体甘露糖苷酶（dLMII）。两种化合物是弱选择性dGMIIb抑制剂，IC50处于毫摩尔水平。此外，还发现另一种GH38酶，即市售的刀豆α-甘露糖苷酶，无论碳水化合物核心如何，均被三唑缀合物抑制，而相应的砜则无活性。