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

Research output: Contribution to journalArticle


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.

Original languageEnglish
Pages (from-to)626-634
Number of pages9
JournalEuropean Journal of Medicinal Chemistry
Publication statusPublished - 2018 Jan 20



  • Combinatorial chemistry
  • Enzyme stabilizer
  • Fabry disease
  • Iminosugar
  • Lysosomal α-galactosidase
  • Trihydroxylated piperidine

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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