Tetravalent glycocyclopeptide with nanomolar affinity to wheat germ agglutinin

Org Biomol Chem. 2013 Nov 7;11(41):7113-22. doi: 10.1039/c3ob41203b.

Abstract

A series of tetravalent glycocyclopeptides functionalized with GlcNAc was synthesized using copper(i)-catalysed alkyne-azide cycloaddition, oxime ligation and thiol-ene coupling. The binding ability of these compounds towards wheat germ agglutinin was studied by a competitive ELLA test and ITC experiments. While all compounds were able to inhibit WGA binding to GlcNAc-polymer coated surfaces at low concentrations, derivative 17 having an aliphatic spacer and thioether linkage was 4.9 × 10(6) times more potent on a per sugar basis than GlcNAc. This remarkably strong effect was confirmed by ITC experiments as these revealed an association constant of 9 nM for this compound, therefore presenting a gain of 200,000 times over GlcNAc. These results for compound 17 represent the highest binding properties reported for WGA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / chemistry
  • Alkynes / chemistry
  • Azides / chemistry
  • Binding Sites / drug effects
  • Calorimetry
  • Catalysis
  • Copper / chemistry
  • Cyclization
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Glycopeptides / chemical synthesis
  • Glycopeptides / chemistry
  • Glycopeptides / pharmacology*
  • Molecular Conformation
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / pharmacology*
  • Polymers / chemistry
  • Structure-Activity Relationship
  • Surface Properties
  • Wheat Germ Agglutinins / antagonists & inhibitors*
  • Wheat Germ Agglutinins / chemistry

Substances

  • Alkynes
  • Azides
  • Glycopeptides
  • Peptides, Cyclic
  • Polymers
  • Wheat Germ Agglutinins
  • Copper
  • Acetylglucosamine