Dissection of Conformationally Restricted Inhibitors Binding to a β-Glucosidase

Tracey M. Gloster, Robert Madsen, Gideon J. Davies

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Glycosidase inhibition, important in the quest for highly potent and specific drugs, can be achieved by mimicking the oxocarbenium ion-like transition-state species that form during the catalytic mechanism. Castanospermine and calystegine B2 are potent inhibitors that are conformationally restricted by the inclusion of ethylene linkers. Their binding to a β-glucosidase from Thermotoga maritima has been studied by structural, kinetic and thermodynamic methods. Although both compounds inhibit with a similar potency, castanospermine derives the majority of its energetic contribution from enthalpy whereas calystegine B2 binding is more entropically driven.

Original languageEnglish
JournalChemBioChem
Volume7
Issue number5
Pages (from-to)738-742
ISSN1439-4227
DOIs
Publication statusPublished - 2006

Keywords

  • Calystegine
  • Castanospermine
  • Glucosidase
  • Inhibitors
  • Transition state

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