Syntheses of sulfated glycopolymers and analyses of their BACE-1 inhibitory activity

Bioorg Med Chem Lett. 2013 Dec 1;23(23):6390-5. doi: 10.1016/j.bmcl.2013.09.057. Epub 2013 Sep 29.

Abstract

The glycopolymers for glycosaminoglycan mimic were synthesized, and the inhibitory effects of Alzheimer's β-secretase (BACE-1) were examined. The regio-selective sulfation was conducted on N-acetyl glucosamine (GlcNAc), and the acrylamide derivatives were synthesized with the consequent sulfated GlcNAc. The glycopolymers were synthesized with acrylamide using radical initiator. The glycopolymer with sulfated GlcNAc showed the strong inhibitory effect on BACE-1, and the inhibitory effects were dependent on the sulfation positions. Especially, glycopolymers carrying 3,4,6-O-sulfo-GlcNAc showed the strong inhibitory effect. The docking simulation suggested that glycopolymers bind to the active site of BACE-1.

Keywords: BACE-1; Glycopolymer; Glycosaminoglycan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / analogs & derivatives*
  • Acetylglucosamine / chemical synthesis
  • Acetylglucosamine / pharmacology*
  • Amyloid Precursor Protein Secretases / antagonists & inhibitors*
  • Amyloid Precursor Protein Secretases / metabolism
  • Aspartic Acid Endopeptidases / antagonists & inhibitors*
  • Aspartic Acid Endopeptidases / metabolism
  • Glycosaminoglycans / chemical synthesis*
  • Glycosaminoglycans / chemistry
  • Glycosaminoglycans / pharmacology*
  • Humans
  • Sulfates / chemical synthesis*
  • Sulfates / chemistry

Substances

  • Glycosaminoglycans
  • Sulfates
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human
  • Acetylglucosamine