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A Microwave-Assisted Direct Heteroarylation of Ketones Using Transition Metal Catalysis
Published on: February 16, 2020
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Ultra-rapid Electrophilic Cysteine Arylation
Bradley M Lipka1, Daniel S Honeycutt1, Gregory M Bassett1
1Department of Chemistry, University of Rhode Island, 140 Flagg Rd, Kingston, Rhode Island 02881, United States.
Journal of the American Chemical Society
|October 19, 2023
Summary
This study introduces a rapid, uncatalyzed method for cysteine arylation using sulfone-activated pyridinium salts. This technique enables fast and selective bioconjugation of peptides and proteins in aqueous buffers.
Area of Science:
- Chemical Biology
- Organic Chemistry
- Bioconjugation Chemistry
Background:
- Efficient bond-forming reactions are essential for bioconjugation.
- Developing rapid and selective chemical methods for modifying biomolecules is a key challenge.
Purpose of the Study:
- To develop a simple and practical strategy for ultra-rapid electrophilic cysteine arylation.
- To achieve stoichiometric bioconjugation of cysteine residues in peptides and proteins.
Main Methods:
- Utilized sulfone-activated pyridinium salts as electrophilic reagents.
- Conducted uncatalyzed reactions in pH 7.0 aqueous buffer at 25 °C.
- Investigated reaction kinetics and selectivity for bioconjugation.
Main Results:
- Achieved exceptionally high rate constants for cysteine arylation (9800 to 320,000 M-1·s-1).
- Demonstrated stoichiometric bioconjugation of micromolar cysteine within minutes or seconds.
- Obtained high conversion and purity in functionalized peptides and proteins due to excellent selectivity.
Conclusions:
- The developed sulfone-activated pyridinium salts provide a powerful tool for rapid and selective cysteine arylation.
- This method facilitates efficient bioconjugation of peptides and proteins under mild, aqueous conditions.
- The chemistry's speed and selectivity offer significant advantages for various biochemical applications.
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