Design, synthesis, and evaluation of α-galactopyranosylceramide mimics promoting Th2 cytokines production

Bioorg Med Chem Lett. 2019 Jun 1;29(11):1357-1362. doi: 10.1016/j.bmcl.2019.03.043. Epub 2019 Mar 27.

Abstract

The binding properties of CD1d/glycolipid/TCR, glycolipid/TCR interactions in particular, have been investigated using docking computation. Accordingly, efficient modification on C-6' of galactose head was recommended in this report to favor the production of Th2 cytokines. The designed glycolipids have been successfully prepared taking advantages of inverse glycosylation procedure, and their abilities to stimulate mouse iNKT cells in vivo have been tested. Compound 9, having p-hydroxyphenylpropionyl amide group on C-6', presented the best result with respect to the selectivity and quantity on Th2-type cytokine IL-4. We found that the increased glycolipid/TCR interaction might be critical in designing new substrate with Th2-biased cytokine production.

Keywords: CD1d; KRN7000; NKT cells; OCH; Th2 cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD1d
  • Cytokines / biosynthesis*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Galactosylceramides / chemical synthesis
  • Galactosylceramides / chemistry
  • Galactosylceramides / pharmacology*
  • Mice
  • Molecular Structure
  • Natural Killer T-Cells
  • Structure-Activity Relationship
  • Th2 Cells

Substances

  • Antigens, CD1d
  • CD1D protein, human
  • Cytokines
  • Galactosylceramides