Novel sulfated gangliosides, high-affinity ligands for neural siglecs, inhibit NADase activity of leukocyte cell surface antigen CD38

Bioorg Med Chem Lett. 2003 Oct 20;13(20):3441-5. doi: 10.1016/s0960-894x(03)00741-8.

Abstract

Three kinds of novel sulfated gangliosides structurally related to the Chol-1 (alpha-series) ganglioside GQ1balpha were synthesized. These sulfated gangliosides were potent inhibitors of NADase activity of leukocyte cell surface antigen CD38. Among the synthetic gangliosides, GSC-338 (II(3)III(6)-disulfate of iso-GM1b) was surprisingly found to be the most potent structure in both the NADase inhibition and MAG-binding activity. The present study indicates that the sulfated gangliosides are useful to study the recognition of the internal tandem sialic acid residues alpha2-3-linked to Gal(II(3)) as well as the siglec-dependent recognition including a terminal sialic acid residue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase / antagonists & inhibitors*
  • ADP-ribosyl Cyclase 1
  • Antigens, CD
  • Carbohydrate Conformation
  • Carbohydrate Sequence
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Gangliosides / chemistry
  • Gangliosides / metabolism
  • Gangliosides / pharmacology*
  • Ligands
  • Molecular Sequence Data
  • NAD+ Nucleosidase / antagonists & inhibitors*
  • Sulfates / chemistry

Substances

  • Antigens, CD
  • Enzyme Inhibitors
  • Gangliosides
  • Ligands
  • Sulfates
  • ADP-ribosyl Cyclase
  • NAD+ Nucleosidase
  • ADP-ribosyl Cyclase 1