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waddington_et_al_for_chemrxiv.pdf (9.31 MB)

Cysteine Borylation in Unprotected Peptides

preprint
submitted on 11.01.2021, 05:48 and posted on 12.01.2021, 06:05 by Mary A. Waddington, Alice Zheng, Julia M. Stauber, Elamar Hakim Moully, Liban M. A. Saleh, Petr Kral, Alexander Spokoyny
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. Discovered Cysborylation proceeds at room temperature and is tolerant to a variety of functional groups present in complex polypeptides. The resultant bioconjugates show no additional toxicity compared to their Cys aryl-based congeners. Finally, we demonstrate how the developed Cys-borylation can enhance the proteolytic stability of the produced peptide bioconjugates while maintaining the binding affinity to a protein target.

Funding

Atomically Precise Nanoparticles with Multivalent Capabilities

National Institute of General Medical Sciences

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History

Email Address of Submitting Author

spokoyny@chem.ucla.edu

Institution

UCLA

Country

USA

ORCID For Submitting Author

0000-0002-5683-6240

Declaration of Conflict of Interest

Authors declare no conflict of interests.