An Organometallic Strategy for Cysteine Borylation

Citations Over TimeTop 10% of 2021 papers

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.

Related Papers

• → Boc Groups as Protectors and Directors for Ir-Catalyzed C−H Borylation of Heterocycles(2009)107 cited
• → Copper-catalyzed dehydrogenative borylation of terminal alkynes with pinacolborane(2016)96 cited
• → Boron Lewis Pair Mediated C–H Activation and Borylation(2021)29 cited
• → Copper-Catalyzed Borylation of Styrenes by 1,8-Diaminonaphthalene-Protected Diboronic Acid(2023)11 cited
• → ChemInform Abstract: Divergent Synthesis of 2,3,5‐Substituted Thiophenes by C—H Activation/Borylation/Suzuki Coupling.(2010)