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Development of Fluorogenic Substrates of α-l-Fucosidase Useful for Inhibitor Screening and Gene-expression Profiling.
Miura, Kazuki; Tsukagoshi, Takumi; Hirano, Takako; Nishio, Toshiyuki; Hakamata, Wataru.
Afiliação
  • Miura K; Department of Chemistry and Life Science, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa-shi, Kanagawa 252-0880, Japan.
  • Tsukagoshi T; Department of Chemistry and Life Science, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa-shi, Kanagawa 252-0880, Japan.
  • Hirano T; Department of Chemistry and Life Science, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa-shi, Kanagawa 252-0880, Japan.
  • Nishio T; Department of Chemistry and Life Science, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa-shi, Kanagawa 252-0880, Japan.
  • Hakamata W; Department of Chemistry and Life Science, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa-shi, Kanagawa 252-0880, Japan.
ACS Med Chem Lett ; 10(9): 1309-1313, 2019 Sep 12.
Article em En | MEDLINE | ID: mdl-31531202
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.

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Diagnostic_studies / Screening_studies Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Diagnostic_studies / Screening_studies Idioma: En Ano de publicação: 2019 Tipo de documento: Article