Iminosugar-Cyclopeptoid Conjugates Raise Multivalent Effect in Glycosidase Inhibition at Unprecedented High Levels

Chemistry. 2016 Apr 4;22(15):5151-5. doi: 10.1002/chem.201600338. Epub 2016 Feb 24.


A series of cyclopeptoid-based iminosugar clusters has been evaluated to finely probe the ligand content-dependent increase in α-mannosidase inhibition. This study led to the largest binding enhancement ever reported for an enzyme inhibitor (up to 4700-fold on a valency-corrected basis), which represents a substantial advance over the multivalent glycosidase inhibitors previously reported. Electron microscopy imaging and analytical data support, for the best multivalent effects, the formation of a strong chelate complex in which two mannosidase molecules are cross-linked by one inhibitor.

Keywords: glycopeptides; glycosidases; iminosugars; inhibitors; multivalency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Glycoside Hydrolases / antagonists & inhibitors*
  • Glycoside Hydrolases / chemistry*
  • Glycoside Hydrolases / pharmacology
  • Imino Sugars / chemistry*
  • Imino Sugars / pharmacology
  • Ligands
  • Peptides, Cyclic / chemistry*
  • alpha-Mannosidase / chemistry*
  • alpha-Mannosidase / pharmacology


  • Enzyme Inhibitors
  • Imino Sugars
  • Ligands
  • Peptides, Cyclic
  • Glycoside Hydrolases
  • alpha-Mannosidase