Probing Multivalent Carbohydrate-Protein Interactions With On-Chip Synthesized Glycopeptides Using Different...

Area of Science:

• Carbohydrate Chemistry
• Biotechnology
• Surface Science

Background:

• Multivalent ligand-protein interactions enhance affinity and specificity compared to single interactions.
• Glycan-protein interactions are vital in biological processes.
• Existing glycan microarray methods often lack defined multivalent presentation.

Purpose of the Study:

• To develop a flexible, cost-efficient, and rapid method for synthesizing spatially defined multivalent glycopeptides on solid supports.
• To investigate the impact of surface functionalization, wettability, accessibility, and flexibility on glycan-lectin interactions.
• To optimize lectin binder discovery by evaluating various parameters like spacing, density, and ligand presentation.

Main Methods:

• Utilized laser-based array technology for *in situ* chemical synthesis of peptide scaffolds on glass slides.
• Employed copper(I)-catalyzed azide-alkyne cycloaddition to attach different monomer sugar azides to scaffolds.
• Functionalized glass slides with polyethylene glycol (PEG) linkers and varied PEG-spacer inclusion in glycopeptides.

Main Results:

• Spatially defined multivalent glycopeptides were successfully synthesized.
• Surface functionalization, wettability, accessibility, and flexibility significantly influence glycan-lectin interactions.
• Different glycan-lectin pairs require specific surface functionalization and spacers for optimal binding affinity.

Conclusions:

• The developed laser-based array technology enables rapid screening and evaluation of parameters influencing glycan-lectin interactions.
• This approach facilitates the identification of optimal lectin binders by fine-tuning surface and ligand presentation.
• The study highlights the importance of tailored surface chemistry and molecular architecture for effective multivalent interactions.