Photo effect on the CD1d-binding ability of azobenzene-attached analogues of α-GalCer

Bioorg Med Chem Lett. 2020 Mar 1;30(5):126960. doi: 10.1016/j.bmcl.2020.126960. Epub 2020 Jan 11.

Abstract

α-Galactosylceramide (α-GalCer) is recognized by the CD1d proteins on antigen-presenting cells at the ceramide moiety and the galactose moiety is presented to iNKT cells, which stimulates the immune responses. However, the immune suppression by repeated injections of α-GalCer has discouraged its development as an anti-cancer agent. To overcome the shortcoming by spatiotemporal restriction of its exposure, we synthesized the photochromic azobenzene-incorporated analogues and tested the photo-immunoregulation effect in its binding to CD1d. FACS analyses indicated that some of these analogues enhanced the affinity to CD1d on photo-irradiation by about 20%. A docking simulation suggests that the photochromic molecule should be bulkier for a clearer discrimination between on and off states.

Keywords: Azobenzene; CD1d; Galactosylceramide; Photo-immunoregulation; iNKT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD1d / chemistry
  • Antigens, CD1d / metabolism*
  • Azo Compounds / chemical synthesis
  • Azo Compounds / metabolism*
  • Azo Compounds / radiation effects
  • Galactosylceramides / chemical synthesis
  • Galactosylceramides / metabolism*
  • Galactosylceramides / radiation effects
  • Humans
  • Mice
  • Molecular Docking Simulation
  • Natural Killer T-Cells / metabolism
  • Protein Binding / radiation effects

Substances

  • Antigens, CD1d
  • Azo Compounds
  • CD1D protein, human
  • Galactosylceramides
  • alpha-galactosylceramide
  • azobenzene