Synthesis of (3S,4S,5S)-trihydroxylpiperidine derivatives as enzyme stabilizers to improve therapeutic enzyme activity in Fabry patient cell lines

Huang Yi Li, Jay Der Lee, Chiao Wen Chen, Ying Chieh Sun, Wei Chieh Cheng

研究成果: 雜誌貢獻文章

摘要

A series of 3S,4S,5S-trihydroxylated piperidines bearing structural diversity at C-2 or C-6 positions has been synthesized and tested to determine their ability to stabilize the activity of recombinant human α-Galactosidase A (rh-α-Gal A). Hit molecules were identified by rapid inhibitory activity screening, and then further investigated for their ability to protect this enzyme from thermo-induced denaturation and enhance its activity in Fabry patient cell lines. Our study resulted in the identification of a new class of small molecules as enzyme stabilizers for the potential treatment of Fabry disease. Of these, stabilizer 21 was the most effective, showing a 12-fold increase in rh-α-Gal A activity in Fabry disease cell lines.

原文英語
頁(從 - 到)626-634
頁數9
期刊European Journal of Medicinal Chemistry
144
DOIs
出版狀態已發佈 - 2018 一月 20

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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