Selection of the biological activity of DNJ neoglycoconjugates through click length variation of the side chain

Org Biomol Chem. 2011 Aug 7;9(15):5373-88. doi: 10.1039/c1ob05119a. Epub 2011 Apr 21.

Abstract

A series of neoglycoconjugates derived from deoxynojirimycin has been prepared by click connection with functionalised adamantanes. They have been assayed as glycosidase inhibitors, as inhibitors of the glycoenzymes relevant to the treatment of Gaucher disease, as well as correctors of the defective ion-transport protein involved in cystic fibrosis. We have demonstrated that it is possible to selectively either strongly inhibit ER-α-glucosidases and ceramide glucosyltransferase or restore the activity of CFTR in CF-KM4 cells by varying the length of the alkyl chain linking DNJ and adamantane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Deoxynojirimycin / chemistry*
  • Animals
  • Antiviral Agents / chemistry*
  • Cell Line
  • Chromatography, High Pressure Liquid
  • Click Chemistry
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Glycoconjugates / chemistry*
  • HL-60 Cells
  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Rats
  • Small Molecule Libraries / chemistry

Substances

  • Antiviral Agents
  • Enzyme Inhibitors
  • Glycoconjugates
  • Small Molecule Libraries
  • 1-Deoxynojirimycin