Cucurbit[6]uril-Promoted Click Chemistry for Protein Modification

Area of Science:

• Supramolecular Chemistry
• Chemical Biology
• Bioconjugation

Background:

• Azide-alkyne cycloaddition is a key reaction for bioconjugate synthesis, with copper(I) or strain-promoted variants widely used.
• Cucurbit[6]uril (CB6)-promoted cycloaddition has been limited to rotaxane synthesis and not applied to complex bioconjugates.

Purpose of the Study:

• To adapt CB6-promoted azide-alkyne cycloaddition into a versatile bioconjugation technique.
• To synthesize novel protein conjugates using optimized CB6 click chemistry.

Main Methods:

• Developed new CB6 click chemistry substrates lacking cross-reactive functional groups.
• Optimized reaction conditions for CB6-promoted azide-alkyne cycloaddition.
• Synthesized various protein conjugates, including protein-peptide, protein-DNA, protein-polymer, and protein-drug.

Main Results:

• CB6 click chemistry was successfully repurposed from rotaxane synthesis to bioconjugation.
• A range of complex protein conjugates were synthesized with high efficiency.
• CB6 click demonstrated compatibility with strain-promoted azide-alkyne cycloaddition for sequential bioconjugation.

Conclusions:

• CB6-promoted click chemistry offers a novel and powerful method for protein bioconjugation.
• This technique facilitates the creation of complex biomaterials for diverse applications.
• CB6 click chemistry expands the toolkit for advanced bioconjugate synthesis.