Pd(II)‐Mediated C−H Activation for Cysteine Bioconjugation. Issue 11 (12th January 2022)

• Record Type: Journal Article
• Authors: Tilden, James A. R.; Lubben, Anneke T.; Reeksting, Shaun B.; Kociok‐Köhn, Gabriele; Frost, Christopher G.
• Is Part Of: Chemistry. Volume 28:Issue 11(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-01-12
• Subjects: bioconjugation -- C−H activation -- cross-coupling -- cysteine -- palladium; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202104385
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Selective bioconjugation remains a significant challenge for the synthetic chemist due to the stringent reaction conditions required by biomolecules coupled with their high degree of functionality. The current trailblazer of transition‐metal mediated bioconjugation chemistry involves the use of Pd(II) complexes prepared via an oxidative addition process. Herein, the preparation of Pd(II) complexes for cysteine bioconjugation via a facile C−H activation process is reported. These complexes show bioconjugation efficiency competitive with what is seen in the current literature, with a user‐friendly synthesis, common Pd(II) sources, and a more cost‐effective ligand. Furthermore, these complexes need not be isolated, and still achieve high conversion efficiency and selectivity of a model peptide. These complexes also demonstrate the ability to selectively arylate a single surface cysteine residue on a model protein substrate, further demonstrating their utility. Abstract : Out of the box : A highly efficient bioconjugation strategy is reported utilising Pd(II) complexes prepared via C−H activation, which enable selective S‐ arylation of cysteine. These C−H activation complexes were prepared using common Pd(II) sources and without the need for a glovebox. A wide substrate scope is enabled by in situ generation of these complexes, which produce excellent conversions of a model tripeptide and are able to arylate surface cysteine on an intact protein.