Induced Bioconjugation via On-Demand Isocyanate Formation

Area of Science:

• Chemical Biology
• Organic Chemistry
• Biochemistry

Background:

• Selective bioconjugation is crucial for precise biomolecular modifications.
• Highly reactive electrophilic warheads like isocyanates face challenges in reactivity, selectivity, and stability.
• Existing methods often struggle with hydrolytic decomposition and require careful control.

Purpose of the Study:

• To develop a novel bioconjugation strategy for on-demand isocyanate generation.
• To overcome the limitations of traditional isocyanate-based labeling methods.
• To enable rapid and selective protein labeling in complex biological environments.

Main Methods:

• A stable hydroxamic acid-pyrrolidine conjugate precursor was synthesized.
• A sulfonyl fluoride activator was used to generate isocyanates in situ.
• Boronic ester formation was utilized for rapid and reversible reaction kinetics.

Main Results:

• The novel strategy generates isocyanates on demand from a stable precursor.
• The method achieved high reaction rates for protein labeling, up to 10^4 M^-1 s^-1.
• Selective and inducible biomolecular labeling in biological systems was demonstrated.

Conclusions:

• The developed
• isocyanate surrogate
• approach offers a practical and versatile tool for bioconjugation.
• This method enables inducible and selective labeling, expanding the toolkit for chemical biology.
• The strategy addresses key challenges associated with traditional isocyanate reactivity and stability.