Chemical synthesis of 4-azido-β-galactosamine derivatives for inhibitors of N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase

Glycoconj J. 2018 Oct;35(5):477-491. doi: 10.1007/s10719-018-9839-2. Epub 2018 Sep 1.

Abstract

Chondroitin sulfate E (CS-E) plays a crucial role in diverse processes ranging from viral infection to neuroregeneration. Its regiospecific sulfation pattern, generated by N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST), is the main structural determinant of its biological activity. Inhibitors of GalNAc4S-6ST can serve as powerful tools for understanding physiological functions of CS-E and its potential therapeutic leads for human diseases. A family of new 4-acylamino-β-GalNAc derivatives and 4-azido-β-GalNAc derivatives were synthesized for their potential application as inhibitors of GalNAc4S-6ST. The target compounds were evaluated for their inhibitory activities against GalNAc4S-6ST. The results revealed that 4-pivaloylamino- and 4-azido-β-GalNAc derivatives displayed evident activities against GalNAc4S-6ST with IC50 value ranging from 0.800 to 0.828 mM. They showed higher activities than benzyl D-GalNAc4S that was used as control.

Keywords: Chemical synthesis; Inhibitor; N-Acetylgalactosamine 4-sulfate 6-O-sulfotransferase; Sulfotransferase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry
  • Animals
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Galactosamine / chemical synthesis*
  • Galactosamine / chemistry
  • Galactosamine / pharmacology*
  • Humans
  • Sulfotransferases / antagonists & inhibitors*
  • Sulfotransferases / metabolism

Substances

  • Amides
  • Enzyme Inhibitors
  • Galactosamine
  • N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase
  • Sulfotransferases