Peptide Release, Side-Chain Deprotection, Work-Up, and Isolation

After having successfully synthesized a peptide, it has to be released from the solid support, unless it is being used for on-resin display. The linker and, in some cases, the cleavage mixture determine the C -terminal functionality of the released peptide. In most cases, the peptide is released with concomitant removal of side-chain protecting groups. However, some combinations of linkers and side-chain protecting groups enable a two-stage procedure, either using orthogonal chemistry or graduated labilities. Herein, we describe protocols for the release of peptides from the most commonly used linker types providing a variety of different C -terminal functionalities, including acids, amides, amines, and aldehydes. Moreover, suggestions for determination of peptide purity and for storage conditions are provided.