Development of α1,6-fucosyltransferase inhibitors through the diversity-oriented syntheses of GDP-fucose mimics using the coupling between alkyne and sulfonyl azide

Bioorg Med Chem. 2017 Jun 1;25(11):2844-2850. doi: 10.1016/j.bmc.2017.02.036. Epub 2017 Feb 28.

Abstract

We developed α1,6-fucosyltransferase (FUT8) inhibitors through a diversity-oriented synthesis. The coupling reaction between the fucose unit containing alkyne and the guanine unit containing sulfonyl azide under various conditions afforded a series of Guanosine 5'-diphospho-β-l-fucose (GDP-fucose) analogs. The synthesized compounds displayed FUT8 inhibition activity. A docking study revealed that the binding mode of the inhibitor synthesized with FUT8 was similar to that of GDP-fucose.

Keywords: Diversity-oriented synthesis; Glycosyltransferase inhibitor; Sulfonyl azide; α1,6-Fucosyltransferase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemistry
  • Alkynes / pharmacology*
  • Azides / chemistry
  • Azides / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Fucosyltransferases / antagonists & inhibitors*
  • Fucosyltransferases / metabolism
  • Guanosine Diphosphate Fucose / chemistry
  • Guanosine Diphosphate Fucose / pharmacology*
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Alkynes
  • Azides
  • Enzyme Inhibitors
  • Guanosine Diphosphate Fucose
  • Fucosyltransferases
  • Glycoprotein 6-alpha-L-fucosyltransferase