A Mild Protecting-Group Free Strategy for Neoglycoconjugate Synthesis

Area of Science:

• Carbohydrate Chemistry
• Chemical Biology
• Bioconjugation

Background:

• Neoglycoconjugates are vital tools for research and therapeutics, mimicking natural structures.
• Conventional synthesis methods often require harsh conditions incompatible with sensitive proteins.
• Developing mild, efficient conjugation strategies is crucial for advancing glycoconjugate applications.

Purpose of the Study:

• To develop a simple, modular, and chemoselective strategy for synthesizing neoglycoconjugates.
• To enable glycan conjugation under mild conditions, avoiding protecting groups.
• To facilitate the preparation of neoglycoconjugates for sensitive or aggregation-prone proteins.

Main Methods:

• A novel chemoselective coupling between unprotected sugars and hydroxylamines under mild acidic conditions.
• Utilizing a terminal alkene as a handle for subsequent conjugation via thiol-ene coupling (TEC).
• Optimization of TEC conditions using various photocatalysts for efficient protein conjugation.

Main Results:

• Successful synthesis of neoglycoconjugates from unprotected N- and O-linked glycans.
• Demonstration of facile protein conjugation using TEC with diverse photocatalysts.
• Application of the method to an aggregation-prone protein, α-synuclein, under mild conditions.

Conclusions:

• The developed strategy offers a protecting-group-free approach for neoglycoconjugate synthesis.
• This method is compatible with sensitive proteins and various glycan types.
• It provides a versatile platform for creating tailored glycoconjugates for biological studies and therapeutic development.