Glycogroup, Deparment of Organic Chemistry, Graz University of Technology, 8010 Graz, Austria.
Chembiochem. 2010 Sep 24;11(14):2026-33. doi: 10.1002/cbic.201000192.
A collection of new reversible glycosidase inhibitors of the iminoalditol type featuring N-substituents containing perfluorinated regions has been prepared for evaluation of physicochemical, biochemical and diagnostic properties. The vast variety of feasible oligofluoro moieties allows for modular approaches to customised structures according to the intended applications, which are influenced by the fluorine content as well as the distance of the fluorous moiety from the ring nitrogen. The first examples, in particular in the D-galacto series, exhibited excellent inhibitory activities. A preliminary screen with two human cell lines showed that, at subinhibitory concentrations, they are powerful pharmacological chaperones enhancing the activities of the catalytically handicapped lysosomal D-galactosidase mutants associated with GM1 gangliosidosis and Morquio B disease.
已经制备了一系列新型的、含有全氟区域的亚氨基糖醇型可逆糖苷酶抑制剂，用于评估物理化学、生化和诊断特性。大量可行的低氟部分允许根据预期应用进行定制结构的模块化方法，这受到氟含量以及氟部分与环氮之间距离的影响。特别是在 D-半乳糖系列中的第一个实例，表现出优异的抑制活性。对两种人类细胞系的初步筛选表明，在亚抑制浓度下，它们是强大的药理学伴侣，可增强与 GM1 神经节苷脂病和 Morquio B 病相关的催化功能障碍溶酶体 D-半乳糖苷酶突变体的活性。
