Dissection of alpha mannosidases: from reaction coordinate to inhibition

α甘露糖苷酶剖析：从反应坐标到抑制

• 批准号: BB/G016127/1
• 负责人: Gideon Davies
• 金额: $ 68.96万
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FG016127%2F1
• 关键词: Dissection; alpha; mannosidases; reaction; coordinate

Sugars are more than just food. Sugars coat all our cells and the cells of our pathogens. The communication between cells, both healthy and pathogenic, both normal and tumour is governed by sugars. Sugars are 'the language of the cell'. The chemical factories that make, modify and tune sugars are called 'enzymes'. The control and organisation of these enzymatic machines is central to the healthy organism and, conversely, their subversion leads to changes in cell growth, auto immune disease and cancers. An unusual sugar, called mannose, is of particular interest to scientists as its chemistry is very difficult (its crowded centres make reactions difficult) and because the enzymes involved in its modification are both highly unusual and implicated in cell division and disease. The aim of this BBSRC grant is to study enzymes involved in mannose chemistry, to dissect them at the three-dimensional level and then to use cunning chemistry to both study their reaction and inspire and analyse inhibitors that should lead to chemical probes of healthy cells and potential therapeutic agents.

糖不仅仅是食物。糖包裹着我们所有的细胞和病原体的细胞。健康细胞和致病细胞、正常细胞和肿瘤细胞之间的交流都是由糖控制的。糖是细胞的语言。制造、修饰和调节糖的化学工厂被称为“酶”。这些酶机器的控制和组织是健康生物体的核心，相反，它们的破坏导致细胞生长，自身免疫疾病和癌症的变化。一种不寻常的糖，称为甘露糖，对科学家特别感兴趣，因为它的化学性质非常困难（其拥挤的中心使反应变得困难），并且因为参与其修饰的酶非常不寻常，并且与细胞分裂和疾病有关。该BBSRC资助的目的是研究参与甘露糖化学的酶，在三维水平上解剖它们，然后使用巧妙的化学方法来研究它们的反应，并激发和分析抑制剂，这些抑制剂应该导致健康细胞和潜在治疗剂的化学探针。

项目成果

Fleetamine (3-O-a-d-glucopyranosyl-swainsonine): the synthesis of a hypothetical inhibitor of endo-a-mannosidase

Fleetamine（3-O-a-d-吡喃葡萄糖基-苦豆素）：合成一种假设的内切-α-甘露糖苷酶抑制剂

• DOI: 10.1016/j.tetasy.2012.06.011
• 发表时间: 2012
• 期刊: Asymmetry
• 作者: Quach T

Structure and kinetic investigation of Streptococcus pyogenes family GH38 alpha-mannosidase.

• DOI: 10.1371/journal.pone.0009006
• 发表时间: 2010-02-03
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Suits MD;Zhu Y;Taylor EJ;Walton J;Zechel DL;Gilbert HJ;Davies GJ
• 通讯作者: Davies GJ