Site-selective lysine conjugation methods and applications towards antibody–drug conjugates. Issue 82 (27th September 2021)

• Record Type: Journal Article
• Authors: Haque, Muhammed; Forte, Nafsika; Baker, James R.
• Is Part Of: Chemical communications. Volume 57:Issue 82(2021)
• Page Start: 10689
• Page End: 10702
• Publication Date: 2021-09-27
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1039/d1cc03976h
• Languages: English
• ISSNs: 1359-7345

Abstract

Abstract : In this feature article we discuss developments in site-selective lysine modification methodologies and their application towards the synthesis of antibody–drug conjugates; including our recent work on a cysteine-to-lysine transfer (CLT) protocol. Abstract : Site-selective protein modification is of significant interest in chemical biology research, with lysine residues representing a particularly challenging target. Whilst lysines are popular for bioconjugation, due to their nucleophilicity, solvent accessibility and the stability of the resultant conjugates, their high abundance means site-selectivity is very difficult to achieve. Antibody–drug conjugates (ADCs) present a powerful therapeutic application of protein modification, and have often relied extensively upon lysine bioconjugation for their synthesis. Here we discuss advances in methodologies for achieving site-selective lysine modification, particularly within the context of antibody conjugate construction, including the cysteine-to-lysine transfer (CLT) protocol which we have recently reported.