Stapling of β-Glucans Increases Antibody Binding

Area of Science:

• Carbohydrate Chemistry
• Structural Biology
• Biochemistry

Background:

• Higher-order structures of biological macromolecules are critical for their function.
• Peptide stapling enhances pharmacological properties by tuning conformational space.
• The 3D structures of glycans are less understood than peptides and oligonucleotides, with limited success in modulating their structure for improved protein binding.

Purpose of the Study:

• To develop a method for stapling β-(1,3)-glucans to control their conformation.
• To mimic the naturally occurring triple helix structure of glucans.
• To investigate the impact of glycan conformation on antibody binding.

Main Methods:

• Automated glycan assembly for synthesizing stapled glycans.
• Solid-phase peptide synthesis for linker construction and ring-closure.
• Molecular dynamics simulations to analyze conformational changes.
• Glycan microarray experiments to assess antibody binding affinity.

Main Results:

• Successfully synthesized stapled β-(1,3)-glucans with tunable conformations.
• Demonstrated that stapling alters the conformational space of glycans.
• Observed significantly enhanced binding of stapled glycans to monoclonal antibodies compared to linear glycans.

Conclusions:

• Controlling the conformational space of short oligosaccharides is achievable through stapling.
• Stapled glycans exhibit improved binding affinity to antibodies.
• This approach offers potential for developing novel synthetic glycans for drug and vaccine development.