Probing the aglycon binding site of a beta-glucosidase: a collection of C-1-modified 2,5-dideoxy-2,5-imino-D-mannitol derivatives and their structure-activity relationships as competitive inhibitors

Bioorg Med Chem. 2004 Jul 1;12(13):3485-95. doi: 10.1016/j.bmc.2004.04.037.

Abstract

A range of new C-1 modified derivatives of the powerful glucosidase inhibitor 2,5-dideoxy-2,5-imino-D-mannitol has been synthesised and their biological activities probed with the beta-glucosidase from Agrobacterium sp. Ki values are compared with those of previously prepared close relatives. Findings suggest dramatic effects exerted by the aglycon binding site on substrate/inhibitor binding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding, Competitive
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Imino Pyranoses
  • Mannitol / analogs & derivatives*
  • Mannitol / chemical synthesis
  • Mannitol / chemistry
  • Mannitol / pharmacology*
  • Molecular Structure
  • Rhizobium / drug effects
  • Rhizobium / enzymology
  • Structure-Activity Relationship
  • beta-Glucosidase / chemistry*
  • beta-Glucosidase / metabolism*

Substances

  • 2,5-dideoxy-2,5-imino-D-mannitol
  • Enzyme Inhibitors
  • Imino Pyranoses
  • Mannitol
  • beta-Glucosidase