Peptide Rearrangement Side Reactions

Undesirable peptide rearrangement represents a category of common side reactions occurring in the process of peptide manufacture as well as storage. Due to the existence of a plethora of functional groups and divergent conditions, e.g. different pH values that the peptide has to be subjected to in the process of manufacture, in combination with somewhat unpredictable synergistic steric effects, peptide rearrangement is prone to take place on some labile individuals under certain circumstances. One of the challenges inherent to these types of side reactions is that the derived side products are frequently isomer to the target peptides, and the development of pertinent analytical methods with respect to the re-arranged peptide impurities hence poses a critical task. Moreover, the rearrangement process might also result in the formation of impurities with a redundantly incorporated residue/segment, which is difficult to be separated from the target product. In order to alleviate the somewhat overwhelming stresses these impurities exert on the downstream process (purification) of peptide production, they should be preferably addressed in the upstream process (synthesis) so as to minimize the occurrences by efficient synthetic strategies. In this chapter, representative rearrangement processes that daunt peptide synthesis are elucidated, and the corresponding potential solutions are discussed.