Reviving old protecting group chemistry for site-selective peptide–protein conjugation. Issue 84 (4th October 2018)

• Record Type: Journal Article
• Authors: Gunnoo, Smita B.; Iyer, Abhishek; Vannecke, Willem; Decoene, Klaas W.; Hebbrecht, Tim; Gettemans, Jan; Laga, Mathias; Loverix, Stefan; Lasters, Ignace; Madder, Annemieke
• Is Part Of: Chemical communications. Volume 54:Issue 84(2018)
• Page Start: 11929
• Page End: 11932
• Publication Date: 2018-10-04
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1039/c8cc06684a
• Languages: English
• ISSNs: 1359-7345

Abstract

Abstract : Unprotected peptides equipped with property enhancing moieties and a Cys(Scm) residue can be site-selectively conjugated to proteins via crossed-disulfide formation. Abstract : Methodologies to conjugate proteins to property-enhancing entities are highly sought after. We report a remarkably simple strategy for conjugating proteins bearing accessible cysteines to unprotected peptides containing a Cys(Scm) protecting group, which is introduced on-resin via a Cys(Acm) building block. The peptides employed for this proof of principle study are highly varied and structurally diverse, and undergo multiple on-resin decoration steps prior to conjugation. The methodology was applied to three different proteins, and proved to be efficient and site-selective. This twist on protecting group chemistry has led to a novel and generally applicable strategy for crossed-disulfide formation between proteins and peptides.