Effect of Azide Position on the Rate of Azido Glucose–Cyclooctyne Cycloaddition

Abstract

The strain-promoted azide–alkyne cycloaddition (SPAAC) is the most widely used bioorthogonal reaction for imaging azide-labeled glycans in living systems. Rapid SPAAC reactions are essential for visualizing biological processes that occur on a short timescale, and efforts to increase SPAAC reaction rates by modulating the cyclooctyne structure have been highly successful. However, optimizing azido sugar structure for improved SPAAC rates has not been explored. In this study, we show that altering azide position on the sugar ring can have a modest but significant impact on SPAAC reaction rate, which has implications for designing and interpreting experiments involving azide-specific bioorthogonal reactions.

Keywords:

• Strain-promoted azide–alkyne cycloaddition (SPAAC)
• Copper-free click chemistry
• Bioorthogonal chemistry
• Reaction kinetics/rate
• Azido sugar