Molecular design of N-linked tetravalent glycosides bearing N-acetylglucosamine, N,N'-diacetylchitobiose and N-acetyllactosamine: Analysis of cross-linking activities with WGA and ECA lectins

Bioorg Med Chem. 2010 Jan 15;18(2):621-9. doi: 10.1016/j.bmc.2009.12.006. Epub 2009 Dec 6.

Abstract

Two types of nonspacer- and spacer-N-linked tetravalent glycosides bearing N-acetylglucosamine (GlcNAc), N,N'-diacetylchitobiose [(GlcNAc)(2)] and N-acetyllactosamine (LacNAc) were designed and prepared as glycomimetics. The interactions of wheat germ (Triticum vulgaris) agglutinin (WGA) and coral tree (Erythrina cristagalli) agglutinin (ECA) with a series of tetravalent glycosides and related compounds were studied using a hemagglutination inhibition assay, a precipitation assay, double-diffusion test, and an optical biosensor based on surface plasmon resonance (SPR). The tetravalent glycosides were found to be capable of binding and precipitating the lectins as tetravalent ligands. Strong interactions with WGA, due to a combination of multivalency effects and spacer effects, were observed for tetravalent glycosides bearing flexible tandem GlcNAc. The chelate effect leads to large rate enhancement for the tetravalent system with favorable orientation of ligands. Our simple strategy produced multivalent glycosides with strong cross-linking activity for lectin as a specific coagulant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / chemistry*
  • Amino Sugars / chemistry*
  • Animals
  • Cross-Linking Reagents / chemistry*
  • Cross-Linking Reagents / pharmacology
  • Disaccharides / chemistry*
  • Drug Design
  • Erythrocytes / drug effects
  • Glycosides / chemistry
  • Hemagglutination Inhibition Tests
  • Molecular Structure
  • Plant Lectins / chemistry*
  • Rabbits
  • Surface Plasmon Resonance
  • Wheat Germ Agglutinins / chemistry*

Substances

  • Amino Sugars
  • Cross-Linking Reagents
  • Disaccharides
  • Glycosides
  • Plant Lectins
  • Wheat Germ Agglutinins
  • erythrina lectin
  • N,N-diacetylchitobiose
  • N-acetyllactosamine
  • Acetylglucosamine