Synthetic heparan sulfate dodecasaccharides reveal single sulfation site interconverts CXCL8 and CXCL12 chemokine biology

Chem Commun (Camb). 2015 Sep 18;51(72):13846-9. doi: 10.1039/c5cc05222j. Epub 2015 Aug 3.

Abstract

The multigram-scale synthesis of a sulfation-site programmed heparin-like dodecasaccharide is described. Evaluation alongside dodecasaccharides lacking this single glucosamine O6-sulfation, or having per-O6-sulfation, shows that site-specific modification of the terminal glucosamine dramatically interconverts regulation of in vitro and in vivo biology mediated by the two important chemokines, CXCL12 (SDF1α) or CXCL8 (IL-8).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbohydrate Sequence
  • Cell Migration Assays, Leukocyte
  • Chemokine CXCL12 / antagonists & inhibitors*
  • Heparitin Sulfate / chemistry*
  • Heparitin Sulfate / pharmacology*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Interleukin-8 / antagonists & inhibitors*
  • Leukocytes
  • Oligosaccharides / chemistry*
  • Oligosaccharides / pharmacology*

Substances

  • CXCL12 protein, human
  • CXCL8 protein, human
  • Chemokine CXCL12
  • Interleukin-8
  • Oligosaccharides
  • Heparitin Sulfate