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A constraint scaffold enhances affinity of a bivalent N-acetylglucosamine ligand against wheat germ agglutinin.

Authors
  • Matsushita, Takahiko1
  • Tsuchibuchi, Koji2
  • Koyama, Tetsuo2
  • Hatano, Ken1
  • Matsuoka, Koji3
  • 1 Area for Molecular Function, Division of Material Science, Graduate School of Science and Engineering, Saitama University, Sakura, Saitama 338-8570, Japan; Medical Innovation Research Unit (MiU), Advanced Institute of Innovative Technology (AIIT), Saitama University, Sakura, Saitama 338-8570, Japan. , (Japan)
  • 2 Area for Molecular Function, Division of Material Science, Graduate School of Science and Engineering, Saitama University, Sakura, Saitama 338-8570, Japan. , (Japan)
  • 3 Area for Molecular Function, Division of Material Science, Graduate School of Science and Engineering, Saitama University, Sakura, Saitama 338-8570, Japan; Medical Innovation Research Unit (MiU), Advanced Institute of Innovative Technology (AIIT), Saitama University, Sakura, Saitama 338-8570, Japan. Electronic address: [email protected] , (Japan)
Type
Published Article
Journal
Bioorganic & medicinal chemistry letters
Publication Date
Apr 19, 2018
Identifiers
DOI: 10.1016/j.bmcl.2018.04.047
PMID: 29691137
Source
Medline
Keywords
License
Unknown

Abstract

Bivalent glycoconjugates have a minimal valence with avidity potential on protein-carbohydrate interactions as well as simplicity of chemical structures enabling simple synthesis with low cost. Understanding the way to maximize the affinities of bivalent glycoconjugates is important for the development of cost-effective tools for therapeutic and diagnostic research. However, there has been little discussion about the effects of constraints imposed from ligand scaffolds on the binding abilities. We synthesized three kinds of biantennary N-acetylglucosamine glycosides with different scaffolds using isobutenyl bis(propargyl)ether as a common scaffold precursor. Decoration of the scaffold branches with GlcNAc moieties through copper-catalyzed azide-alkyne cycloaddition and grafting of the alkenyl focal point to another bivalent biotin dendron through thiol-ene and nucleophilic substitution reactions were successfully carried out in an orthogonal manner. The association constants of the ligands against wheat germ agglutinin were determined by a fluorometric titration assay. A bivalent biotin counterpart provided higher affinity than an isobutyl scaffold, whereas an isobutenyl scaffold yielded more enhancement than a bivalent biotin counterpart. The present work suggested that the constraint and steric bulk of ligand scaffolds are possible factors for improving binding properties of glycoconjugates against lectins or proteins.

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