Manual solid phase synthesis of potent peptide analogs

Expression of proteins in E. coli is often employed to obtain protein samples; nevertheless, not all protein fragments can be cloned. Automatic and semiautomatic peptide synthesizers have been developed to efficiently synthesize peptides on a solid phase. However, the high cost limits general application for many peptide-related research projects. Therefore, we designed an experimental and instrumental setup for the manual synthesis of various peptides and peptidomimetics. We now report the manual synthesis of a phosphopeptide SHC(pY), DDPSpYVNVQ, which is a potent ligand for the Grb2 SH2 domain and plays an important role in signal transduction. We demonstrate that this methodology can be applied to manually synthesize various peptide analogs in a small research laboratory.