Protein-protein interactions (PPIs) are highly attractive drug targets due to their importance in cellular signalling, and their frequent alteration in a variety of disease states, including cancer (e.g. p53-MDM2 interaction) and cardiovascular disease (e.g. cAMP signalling pathways). Modulation of the interaction between two proteins in a signalling pathway can facilitate a beneficial effect in a range of disorders, many of which were previously considered to be extremely challenging therapeutic targets. Compared with small molecules, peptides offer a more realistic option for the development of selective and potent inhibitors of intracellular PPIs. However, the preparation of stable peptide systems remains challenging even though new methods for the stapling of peptide a-helices, or for the formation of (multi)cyclic peptides have emerged. We have developed a simple yet effective method for stapling, cyclising and selectively tagging sulphur and oxygen amino acid side chains with a variety of different perfluoro-heteroaromatics. Our approach allows the generation of highly diverse cyclic and multi-cyclic peptides scaffold libraries and it offers a new platform of the development of PPi inhibitors. Examples of our recent work in the area will be presented.