A facile synthetic approach to L- and P-selectin blockers via copolymerization of vinyl monomers constructing the key carbohydrate modules of sialyl LewisX mimics

Biomacromolecules. 2000 Spring;1(1):68-74. doi: 10.1021/bm990011o.

Abstract

A highly practical synthetic approach is described for artificial L- and P-selectin blockers. The synthesis involves radical bi- and terpolymerizations of p-(N-acrylamido)phenyl 3- or/and 6-sulfo-beta-D-galactoside with allyl alpha-L-fucoside in the presence of acrylamide. Each of the two glycosyl monomers constructs a key carbohydrate module responsible for selectins/sulfated sialyl LewisX (sLeX) bindings. Whereas an acrylamide copolymer carrying 3-sulfo-galactoside showed no activity for any selectins, the fucosylated terpolymer showed a potent activity to block both of P- and L-selectins/sLeX binding at a concentration of a few micrograms per milliliter. The enhanced activity is apparently ascribed to the cooperative binding effects of the fucoside and the 3-sulfo-galactoside residues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbohydrate Sequence
  • Carbohydrates / chemical synthesis*
  • Carbohydrates / pharmacology
  • Fucose / chemistry
  • Indicators and Reagents
  • L-Selectin / metabolism*
  • Magnetic Resonance Spectroscopy
  • Molecular Sequence Data
  • Oligosaccharides / chemistry*
  • P-Selectin / metabolism*
  • Polymers / chemical synthesis
  • Sialyl Lewis X Antigen
  • Structure-Activity Relationship
  • Vinyl Compounds / chemical synthesis*
  • Vinyl Compounds / pharmacology

Substances

  • Carbohydrates
  • Indicators and Reagents
  • Oligosaccharides
  • P-Selectin
  • Polymers
  • Sialyl Lewis X Antigen
  • Vinyl Compounds
  • L-Selectin
  • Fucose