Glycosidase inhibition by ring-modified castanospermine analogues: tackling enzyme selectivity by inhibitor tailoring

Matilde Aguilar-Moncayo, Tracey M. Gloster, Johan P. Turkenburg, M. Isabel Garcia-Moreno, Carmen Ortiz Mellet, Gideon J. Davies, Jose M. Garcia Fernandez

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

Abstract

Synthesis of a panel of iso(thio)urea-type ring-modified castanospermine analogues bearing a freely mutarotating pseudoanomeric hydroxyl group results in tight-binding beta-glucosidase inhibitors with unusual binding signatures; the presence of an N-octyl substituent imparts a remarkable anomeric selectivity, promoting strong binding of the appropriate beta-anomer by the beta-glucosidase.

Original languageEnglish
Pages (from-to)2738-2747
Number of pages10
JournalOrganic & Biomolecular Chemistry
Volume7
Issue number13
DOIs
Publication statusPublished - 2009

Keywords

  • BETA-GLUCOSIDASE
  • TRANSITION-STATE
  • BIOLOGICAL EVALUATION
  • GLYCOGEN-PHOSPHORYLASE
  • CYCLODEXTRIN ANALOGS
  • MOLECULAR-BASIS
  • HIGHLY POTENT
  • BINDING
  • GLYCOMIMETICS
  • ISOFAGOMINE

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