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Homogeneous Glycoconjugate Produced by Combined Unnatural Amino Acid Incorporation and Click-Chemistry for Vaccine Purposes
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High molecular weight polyglycerol-based multivalent mannose conjugates.

Jayachandran N Kizhakkedathu1, A Louise Creagh, Rajesh A Shenoi

  • 1Centre for Blood Research, Department of Pathology and Laboratory Medicine, Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.

Biomacromolecules
|September 1, 2010
PubMed
Summary
This summary is machine-generated.

We created multivalent mannose conjugates using hyperbranched polyglycerols (HPG). These HPG-mannose compounds significantly enhanced binding interactions, showing potential for improved biological applications.

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Area of Science:

  • Carbohydrate Chemistry
  • Polymer Science
  • Bioconjugation

Background:

  • Multivalent carbohydrate-protein interactions are crucial in biological processes.
  • Designing synthetic glycoconjugates with enhanced binding avidity is a key challenge.

Purpose of the Study:

  • To synthesize and characterize multivalent mannose conjugates based on high molecular weight hyperbranched polyglycerols (HPG).
  • To investigate the influence of scaffold size and ligand density on binding interactions with Concanavalin A (Con A).

Main Methods:

  • Synthesis of HPG-mannose conjugates with varying molecular weights (up to 493 kDa) and mannose densities (22-303 units per HPG).
  • Hemagglutination assays using human red blood cells.
  • Isothermal titration calorimetry (ITC) to quantify binding affinity and thermodynamics.

Main Results:

  • HPG-mannose conjugates demonstrated a significant enhancement in relative potency (up to 40,000-fold) and activity per sugar (up to 255-fold) in hemagglutination assays.
  • Binding affinity to Con A was substantially increased, with both molecular size and ligand density playing critical roles.
  • Positive cooperativity in Con A binding was observed for high molecular weight HPG-mannose conjugates.

Conclusions:

  • High molecular weight HPG scaffolds effectively enhance mannose binding interactions with Con A.
  • The observed binding enhancement is attributed to multivalent effects, including inter- and intramolecular interactions and favorable entropic contributions.
  • These findings highlight the potential of HPG-based glycoconjugates for applications requiring specific carbohydrate recognition.