Modified minimal-size fragments of heparan sulfate as inhibitors of endosulfatase-2 (Sulf-2)

Chem Commun (Camb). 2024 Jan 4;60(4):436-439. doi: 10.1039/d3cc02565a.

Abstract

Sulf-2 has been identified as a putative target for anticancer therapies. Here we report the design and synthesis of sulfated disaccharide inhibitors based on IdoA(2S)-GlcNS(6S). Trisulfated disaccharide inhibitor IdoA(2S)-GlcNS(6Sulfamate) demonstrated potent Sulf-2 inhibition. The IC50 value was determined to be 39.8 μM ± 18.3, which is comparable to a tetrasaccharide inhibitor of HSulf-1 reported in the literature. We propose that the disaccharide IdoA(2S)-GlcNS(6S) is the shortest fragment size required for effective inhibition of the Sulfs.

MeSH terms

  • Disaccharides / pharmacology
  • Heparitin Sulfate* / pharmacology
  • Oligosaccharides* / pharmacology
  • Sulfotransferases

Substances

  • Heparitin Sulfate
  • Oligosaccharides
  • Disaccharides
  • Sulfotransferases