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An Organometallic Strategy for Cysteine Borylation
- Source :
- J Am Chem Soc
- Publication Year :
- 2021
- Publisher :
- American Chemical Society (ACS), 2021.
-
Abstract
- Synthetic bioconjugation at cysteine (Cys) residues in peptides and proteins has emerged as a powerful tool in chemistry. Soft nucleophilicity of the sulfur in Cys renders an exquisite chemoselectivity with which various functional groups can be placed onto this residue under benign conditions. While a variety of reactions have been successful at producing Cys-based bioconjugates, the majority of these feature sulfur-carbon bonds. We report Cys-borylation, wherein a benchtop stable Pt(II)-based organometallic reagent can be used to transfer a boron-rich cluster onto a sulfur moiety in unprotected peptides forging a boron-sulfur bond. Cys-borylation proceeds at room temperature and tolerates a variety of functional groups present in complex polypeptides. Further, the bioconjugation strategy can be applied to a model protein modification of Cys-containing DARPin (designed ankyrin repeat protein). The resultant bioconjugates show no additional toxicity compared to their Cys alkyl-based congeners. Finally, we demonstrate how the developed Cys-borylation can enhance the proteolytic stability of the resultant peptide bioconjugates while maintaining the binding affinity to a protein target.
- Subjects :
- Boron Compounds
chemistry.chemical_classification
Bioconjugation
Molecular Structure
Chemistry
Peptide
General Chemistry
010402 general chemistry
01 natural sciences
Biochemistry
Combinatorial chemistry
Borylation
Article
Catalysis
0104 chemical sciences
Residue (chemistry)
Colloid and Surface Chemistry
DARPin
Organometallic Compounds
Moiety
Cysteine
Chemoselectivity
Platinum
Subjects
Details
- ISSN :
- 15205126 and 00027863
- Volume :
- 143
- Database :
- OpenAIRE
- Journal :
- Journal of the American Chemical Society
- Accession number :
- edsair.doi.dedup.....44d506c81de21db6fb7c21e7917d2683