Fucosyltransferase-specific inhibition via next generation of fucose mimetics

Chem Commun (Camb). 2021 Jan 28;57(9):1145-1148. doi: 10.1039/d0cc04847j. Epub 2021 Jan 7.

Abstract

The ability to custom-modify cell surface glycans holds great promise for treatment of a variety of diseases. We propose a glycomimetic of l-fucose that markedly inhibits the creation of sLeX by FTVI and FTVII, but has no effect on creation of LeX by FTIX. Our findings thus indicate that selective suppression of sLex display can be achieved, and STD-NMR studies surprisingly reveal that the mimetic does not compete with GDP-fucose at the enzymatic binding site.

MeSH terms

  • Cell Line, Tumor
  • Fucose / analogs & derivatives*
  • Fucose / chemistry
  • Fucose / pharmacology*
  • Fucosyltransferases / antagonists & inhibitors*
  • Gene Expression Regulation, Enzymologic / drug effects
  • Humans
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / enzymology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma

Substances

  • Fucose
  • Fucosyltransferases