Ascorbate as a pro-oxidant: mild N-terminal modification with vinylboronic acids

Area of Science:

• Organic Chemistry
• Biochemistry
• Chemical Biology

Background:

• Vinylboronic acids are versatile reagents in organic synthesis.
• Protein modification is crucial for biochemical studies and therapeutic development.
• Selective functionalization of proteins remains a challenge.

Purpose of the Study:

• To explore the divergent reactivity of vinylboronic acids for protein modification.
• To develop mild and selective methods for protein functionalization.
• To demonstrate the utility of vinylboronic acids in bioconjugation.

Main Methods:

• Copper-catalyzed N-H modification of protein backbones.
• Ascorbate-mediated N-terminal functionalization in air.
• Application of these methods to human insulin B chain modification.

Main Results:

• Demonstrated dual reactivity of vinylboronic acids: backbone N-H and N-terminal functionalization.
• Achieved selective single-modification of the human insulin B chain.
• Established mild, aqueous reaction conditions compatible with biomolecules.

Conclusions:

• Vinylboronic acids provide a versatile platform for selective protein modification.
• The developed methods offer new tools for bioconjugation and protein engineering.
• This work expands the scope of vinylboronic acid chemistry in biological systems.