4.6 Article

Hexavalent thiofucosides to probe the role of the Aspergillus fumigatus lectin FleA in fungal pathogenicity

期刊

ORGANIC & BIOMOLECULAR CHEMISTRY
卷 19, 期 14, 页码 3234-3240

出版社

ROYAL SOC CHEMISTRY
DOI: 10.1039/d1ob00152c

关键词

-

资金

  1. SATT OUEST VALORISATION
  2. French National Research Agency (Glyco@Alps) [ANR-15-IDEX-02]
  3. Centre National de la Recherche Scientifique (CNRS)

向作者/读者索取更多资源

In this study, potent FleA antagonists were developed based on optimized and non-hydrolysable thiofucoside ligands. Through synthesis and crystallographic analysis, a compound with significantly enhanced binding affinity was obtained, which can be used to explore the role of FleA in the infection process.
Aspergillus fumigatus is a pathogenic fungus infecting the respiratory system and responsible for a variety of life-threatening lung diseases. A fucose-binding lectin named FleA which has a controversial role in A. fumigatus pathogenesis was recently identified. New chemical probes with high affinity and enzymatic stability are needed to explore the role of FleA in the infection process. In this study, we developed potent FleA antagonists based on optimized and non-hydrolysable thiofucoside ligands. We first synthesized a set of monovalent sugars showing micromolar affinity for FleA by isothermal titration calorimetry. The most potent derivative was co-crystallized with FleA to gain insights into the binding mode in operation. Its chemical multimerization on a cyclodextrin scaffold led to an hexavalent compound with a significantly enhanced binding affinity (K-d = 223 +/- 21 nM) thanks to a chelate binding mode. The compound could probe the role of bronchial epithelial cells in a FleA-mediated response to tissue invasion.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据