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An Organometallic Strategy for Cysteine Borylation
Mary A Waddington1, Xin Zheng2, Julia M Stauber1
1Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Drive East, Los Angeles, California 90095, United States.
Journal of the American Chemical Society
|June 1, 2021
Summary
Researchers developed Cys-borylation, a new method for attaching boron clusters to peptides and proteins at cysteine residues. This technique enhances proteolytic stability and maintains binding affinity without increasing toxicity.
Area of Science:
- Chemical Biology
- Organic Chemistry
- Biochemistry
Background:
- Synthetic bioconjugation at cysteine (Cys) residues is crucial in chemistry.
- Existing methods primarily form sulfur-carbon bonds.
- There is a need for novel bioconjugation strategies with diverse bond formations.
Purpose of the Study:
- To introduce Cys-borylation, a novel method for creating boron-sulfur bonds at Cys residues.
- To demonstrate the utility of Cys-borylation in modifying peptides and proteins.
- To evaluate the properties of Cys-borylated bioconjugates.
Main Methods:
- Utilized a benchtop stable Pt(II)-based organometallic reagent for Cys-borylation.
- Applied the method to unprotected peptides and a model protein (DARPin).
- Assessed bioconjugate properties including toxicity and proteolytic stability.
Main Results:
- Successfully formed boron-sulfur bonds at Cys residues under mild conditions.
- Cys-borylation tolerated various functional groups in complex polypeptides.
- Modified DARPin showed no increased toxicity compared to Cys alkyl-based conjugates.
- Enhanced proteolytic stability of peptide bioconjugates was observed.
Conclusions:
- Cys-borylation is a versatile and effective bioconjugation strategy.
- The method offers advantages in enhancing peptide/protein stability and function.
- This approach expands the toolkit for creating novel sulfur-based bioconjugates.
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