Structural basis of multivalent binding to wheat germ agglutinin.

@article{Schwefel2010StructuralBO,
  title={Structural basis of multivalent binding to wheat germ agglutinin.},
  author={David Schwefel and Caroline Maierhofer and Johannes G. Beck and Sonja Seeberger and Kay Diederichs and Heiko M. M{\"o}ller and Wolfram Welte and Valentin Wittmann},
  journal={Journal of the American Chemical Society},
  year={2010},
  volume={132 25},
  pages={
          8704-19
        }
}
The inhibition of carbohydrate-protein interactions by tailored multivalent ligands is a powerful strategy for the treatment of many human diseases. Crucial for the success of this approach is an understanding of the molecular mechanisms as to how a binding enhancement of a multivalent ligand is achieved. We have synthesized a series of multivalent N-acetylglucosamine (GlcNAc) derivatives and studied their interaction with the plant lectin wheat germ agglutinin (WGA) by an enzyme-linked lectin… Expand
Mechanism of multivalent carbohydrate-protein interactions studied by EPR spectroscopy.
TLDR
The application of electron paramagnetic resonance (EPR) spectroscopy of spin-labeled ligands for this purpose is described and structural evidence for chelating binding of a multivalent GlcNAc derivative to WGA in solution is provided. Expand
Mechanistic Insight into Nanomolar Binding of Multivalent Neoglycopeptides to Wheat Germ Agglutinin.
TLDR
To unravel the structural features of this ligand required for high-affinity binding to WGA, a series of cyclic and linear neoglycopeptides are synthesized that differ in their conformational freedom as well as the number of GlcNAc residues. Expand
A constraint scaffold enhances affinity of a bivalent N-acetylglucosamine ligand against wheat germ agglutinin.
TLDR
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. Expand
High-affinity multivalent wheat germ agglutinin ligands by one-pot click reaction
TLDR
Molecular modeling studies, in which the chitobiose moieties were fitted into crystallographically determined binding sites of WGA, correlate the binding enhancements of the multivalent ligands with their ability to bind to the protein in a chelating mode, finding the best WGA ligand a trivalent cluster with an IC50 value of 220 nM. Expand
Glycoclusters as lectin inhibitors: comparative analysis on two plant agglutinins with different folding as a step towards rules for selectivity
Abstract The emerging physiological significance of carbohydrate (glycan)–protein (lectin) recognition engenders the interest to design synthetic inhibitors with a high level of selectivity amongExpand
Bridging lectin binding sites by multivalent carbohydrates.
TLDR
This article summarizes recent examples of chelating lectin ligands of different size and suggests that chelates binding of the discussed ligands is likely, but experimental proof, for example by X-ray crystallography, is limited to only a few cases. Expand
Peptidoglycan Recognition by Wheat Germ Agglutinin. A View by NMR
Wheat germ agglutinin (WGA) is a lectin composed of 4 homologous hevein domains. It has been shown that WGA binds N-acetyl glucosamine (GlcNAc)-related oligosaccharides and has applications asExpand
Rational design and synthesis of optimized glycoclusters for multivalent lectin-carbohydrate interactions: influence of the linker arm.
TLDR
Improved and unprecedented affinities for one of the monovalent probes (K(d)=5.8 μM) and also for a number of the tetravalent compounds that provide several new nanomolar ligands for this tetrameric lectin. Expand
Probing the nature of the cluster effect observed with synthetic multivalent galactosides and peanut agglutinin lectin.
TLDR
Results suggest that the cluster effect that operates in ELLA with the multimers is not related to additional PNA stabilizations and can be ascribed to local concentration effects that favor a dynamic turnover of the tethered galactosides in the PNA binding sites. Expand
Folding and homodimerization of wheat germ agglutinin.
TLDR
A thermodynamic characterization of WGA folding and self-association processes as a function of pH and temperature by using differential scanning and isothermal dilution calorimetry shows the emerging molecular picture for the WGA assembly highlights the need for a reexamination of existing ligand-binding data in the literature. Expand
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