GlyConnect-Ugi: site-selective, multi-component glycoprotein conjugations through GlycoDelete expressed glycans

Area of Science:

• Bioconjugation Chemistry
• Glycoprotein Chemistry
• Organic Synthesis

Background:

• The GlycoDelete (GD) technology provides access to glycoproteins with homogeneous single N-glycans.
• These glycans serve as unique handles for site-selective protein conjugation due to their homogeneous and hydrophilic nature.
• Previous GlyConnect-oxime (GC) strategy utilized oxime formation or reductive amination for single-molecule conjugation.

Purpose of the Study:

• To explore multicomponent reactions (MCR), specifically Ugi and Passerini reactions, for glycan-directed protein conjugation.
• To develop an advanced site-specific protein conjugation strategy, termed MC-GC, building upon GD technology.

Main Methods:

• Application of Ugi and Passerini multicomponent reactions for conjugation.
• Utilizing GlycoDelete glycans as anchors for site-specific protein modification.
• Chemo-enzymatic and chemical pathways for conjugation.

Main Results:

• Successful implementation of Ugi and Passerini reactions for glycan-directed protein conjugation.
• Demonstration of MC-GC as an extension of GD and GC technologies.
• Potential for introducing multiple functional groups in a single step via MCR.

Conclusions:

• Multicomponent reactions offer a powerful approach for site-specific protein conjugation via GlycoDelete glycans.
• The MC-GC strategy enables the creation of hydrophilic, peptide-like linkers.
• This method expands the toolkit for advanced bioconjugation and glycoprotein engineering.