Perfluoroaryl and Perfluoroheteroaryl Reagents as Emerging New Tools for Peptide Synthesis, Modification and Bioconjugation

Brittain, William D.G.; Coxon, Christopher R.

Abstract

Perfluoroaromatic and perfluoroheteroaromatic reagents have emerged in recent years as powerful reagents for peptide and protein modification. Dominated by their regio- and chemoselective nucleophilic aromatic substitution chemistry under mild conditions, they have been used in peptide synthesis, tagging, cyclisation, stapling and protein bioconjugation. Peptides and proteins are becoming increasingly valuable as medicines, diagnostic agents and as tools for biomedical sciences. Much of this has been underpinned by the emergence of new methods for the manipulation and augmentation of native biomolecules. Perfluoroaromatic reagents are perhaps one of the most diverse and exciting tools with which to modify peptides and proteins, due principally to their nucleophilic substitution chemistry, high electron deficiency and the ability for their reactivity to be tuned towards specific nucleophiles. As discussed in this minireview, in recent years, perfluoroaromatic reagents have found applications as protecting groups or activating groups in peptide synthesis and as orthogonal handles for peptide modification. Furthermore, they have applications in chemoselective ‘tagging’, stapling and bioconjugation of peptides and proteins, as well as tuning of ‘drug-like’ properties. This review will also explore possible future applications of these reagents in biological chemistry.

Citation

Brittain, W. D., & Coxon, C. R. (2022). Perfluoroaryl and Perfluoroheteroaryl Reagents as Emerging New Tools for Peptide Synthesis, Modification and Bioconjugation. Chemistry - A European Journal, 28(7), 10-23. https://doi.org/10.1002/chem.202103305

• Journal Article Type: Article
• Acceptance Date: Nov 11, 2021
• Online Publication Date: Nov 11, 2021
• Publication Date: 2022-02
• Deposit Date: Feb 16, 2022
• Publicly Available Date: Feb 16, 2022
• Journal: Chemistry - A European Journal
• Print ISSN: 0947-6539
• Electronic ISSN: 1521-3765
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 28
• Issue: 7
• Pages: 10-23
• DOI: https://doi.org/10.1002/chem.202103305