Abstract
Bioactive peptides are catching great interests for the last few decades. They find several applicationssuch as preservatives in food chemistry and also as therapeutics. There are actually more than 60bioactive peptides on the pharmaceutical market and this figure shows a yearly increase. Among thesepeptides approximately 2/3 are composed of macrocylic structures. This shape indeed usually improvesthe bioactivity of the peptides, their stability and their pharmacokinetic properties.[1]If some of those therapeutic peptides are cyclic analogues of linear compounds, some of them arenatural cyclic peptides that can be found in various living organisms. In both cases, it is essential todevelop robust, efficient and sensitive techniques to determine their structures and/or their quality aftersynthesis or purification as natural extracts. Depending on the origin of the compounds and, eventuallyon the synthetic procedure, peptides may have different forms that can lead to complications for thestructural analysis.We have performed multistage mass spectrometric experiments on a quadrupole ion trap to evaluatethe potential of CID MS/MS and Energy-Resolved Mass Spectrometry (ER-MS) for extensive structuralinformation. Experiments were conducted on purely synthetic model peptides consisting in either simplemacrocycles obtained by intramolecular end-to-end cyclization using click-chemistry [2] or withsynthetic analogues of natural venom peptides from cone snails.[3]We have determined that an increase in the amount of structural information can be obtained: 1) bycareful and appropriate tuning of the mass spectrometer CID conditions[4,5], and 2) by using specificmethodologies such as the «Gas-Phase Collisional Purification»[6-8]. Here we show some preliminaryresults towards this direction.References1. A. Zorzi, K. Deyle, C. Heinis; Curr. Op. Chem. Bio., 38, 24-29 (2017)2. D. Jeanne Dit Fouque et al.; Anal. Bioanal. Chem., 410, 5765-5777 (2018)3. J. Giribaldi et al.; Marine Drugs, 18, 150-163 (2020)4. T.S. Neugebauer, A. Memboeuf; J. Am. Soc. Mass Spectrom., 32, 2685-2697 (2021)5. A. Révész et al.; J. Proteome Res., 17, 5, 1898-1906 (2018)6. D. Jeanne Dit Fouque, A. Maroto, A. Memboeuf; Anal. Chem., 88, 10821-10825 (2016)7. A. Maroto, D. Jeanne Dit Fouque, A.Memboeuf; J. Mass Spectrom.; 1-11 (2020)8. E. Logerot, G.Cazals, A. Memboeuf, C.Enjalbal; Anal. Biochem., 655, 114823 (2022)