CHAPTER 12: Mass Spectrometric Analysis of Cyclic Peptides

Cyclic peptides are a group of polypeptides that have their amino termini, carboxyl termini, or side chains linked via covalent bonds to from a ring structure. Cyclic peptides produced by living organisms are of increasing interest to the biomedical community, as these natural products often possess potent biological and pharmacological activities; e.g., bleomycin in cancer treatment, gramicidin S as an antibiotic against bacteria and some fungi; vancomycin to treat bacterial infections; the lipopeptides surfactin and iturin A with biosurfactant and antibiotic activities, and cyclosporin as a widely used immunosuppressant drug. In terms of economic value, in 2010, the global peptide drug market was predicted to increase by 80% by 2018, to an estimated US$25.4 billion. The above therapeutics and other examples demonstrate the potential of cyclic peptides for therapeutic applications; nevertheless, research on cyclic peptides is still in the early stages and the true potential of these molecules has not yet been fully explored. This chapter describes the structural analysis of cyclic peptides by mass spectrometry, including ionization and ion activation techniques, fragmentation reactions, structural elucidation strategies, as well as selected applications.