Engineering chemical reactivity on cell surfaces through oligosaccharide biosynthesis

Area of Science:

• Biochemistry
• Chemical Biology
• Cell Biology

Background:

• Cell surface oligosaccharides play crucial roles in biological recognition.
• Modifying cell surface chemistry enables new functionalization strategies.
• Metabolic incorporation of unnatural sugars offers a route to novel cell surface functionalities.

Purpose of the Study:

• To develop a method for metabolically incorporating ketone groups onto cell surfaces.
• To demonstrate the utility of cell surface ketone groups for selective chemical ligation.
• To showcase the potential of this technology in applications like targeted drug delivery.

Main Methods:

• Metabolic incorporation of an unnatural N-acetyl-mannosamine derivative containing a ketone group into cell surface oligosaccharides.
• Selective covalent ligation of ketone groups with hydrazide-functionalized molecules under physiological conditions.
• Demonstration of targeted cell killing using ricin A chain-avidin conjugate mediated by cell surface biotinylation.

Main Results:

• Successfully generated cells displaying ketone groups on their surface via metabolic glycoengineering.
• Validated the ability to selectively conjugate hydrazide-bearing molecules to cell surface ketone groups.
• Achieved targeted cell decoration with biotin and subsequent selective cell killing, demonstrating drug delivery potential.

Conclusions:

• Metabolic glycoengineering provides a powerful tool for introducing ketone functionalities onto cell surfaces.
• Cell surface ketone groups enable selective chemical remodeling for diverse biological applications.
• This technology holds promise for advancing targeted therapies and cell-based assays.