Development of Fluorogenic Substrates of α- L -Fucosidase Useful for Inhibitor Screening and Gene-expression Profiling

Kazuki Miura, Takumi Tsukagoshi, Takako Hirano, Toshiyuki Nishio, Wataru Hakamata

研究成果: Article査読

6 被引用数 (Scopus)

抄録

Inhibitors of human α-l-fucosidases, tissue α-l-fucosidase (tFuc), and plasma α-l-fucosidase reportedly play roles in multiple diseases, suggesting their therapeutic potential for gastric disease associated with Helicobacter pylori and fucosidosis. Terminal fucose linkages on glycoproteins and glycolipids are a natural substrate for both enzymes; however, there are currently no fluorogenic substrates allowing their cellular evaluation. Here, we described the development of novel three-color fluorogenic substrates for lysosome-localized tFuc that exhibited excellent specificity and sensitivity in three human cell lines. Additionally, we developed a cell-based high-throughput inhibitor screening system in a 96-well format and a cell-based inhibitory activity evaluation system in a 6-well format for tFuc inhibitors using this substrate, which allowed accurate quantification of the inhibition rate. Moreover, analysis of significant changes in gene expression resulting from 30% inhibition of tFuc in HeLa cells revealed potential roles in gastric disease.

本文言語English
ページ(範囲)1309-1313
ページ数5
ジャーナルACS Medicinal Chemistry Letters
10
9
DOI
出版ステータスPublished - 2019 9月 12
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 創薬
  • 有機化学

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