Automated Glycan Assembly in a Variable-Bed Flow Reactor Provides Insights into Oligosaccharide-Resin Interactions

Area of Science:

• Carbohydrate Chemistry
• Chemical Engineering
• Biotechnology

Background:

• Solid-phase synthesis is crucial for producing complex carbohydrates like oligosaccharides.
• Monitoring resin behavior and molecule solvation is essential for optimizing synthesis efficiency.
• Existing monitoring techniques may not capture dynamic changes during automated synthesis.

Purpose of the Study:

• To adapt a peptide synthesis reactor for automated glycan assembly.
• To investigate resin swelling, growth, and saccharide solvation during solid-phase oligosaccharide synthesis.
• To establish a new method for real-time monitoring of glycan synthesis.

Main Methods:

• Utilized a pressure-based variable-bed flow reactor designed for peptide synthesis.
• Adapted the reactor for automated oligosaccharide synthesis on solid support.
• Monitored resin swelling, coupling efficiencies, and saccharide solvation in real-time.

Main Results:

• Successfully adapted the flow reactor for automated glycan assembly.
• Determined coupling efficiencies and resin growth patterns during synthesis.
• Provided the first estimation of on-resin oligosaccharide solvation.

Conclusions:

• The adapted flow reactor is effective for automated glycan assembly.
• Real-time monitoring of resin swelling and solvation offers insights into synthesis dynamics.
• This approach provides an alternative to traditional UV-vis monitoring for glycan synthesis.