Fundamental Aspects of SPPS and Green Chemical Peptide Synthesis

This perspective essay will briefly recount fundamental physicochemical properties of the peptide-resin that have led to the almost universal use of stepwise solid phase peptide synthesis (SPPS) for the chemical synthesis of peptides. The essay discusses multiple aspects that must be addressed if we are to develop truly green chemical peptide synthesis. An optimal SPPS approach that retains the advantages inherent to polymer-supported chemical synthesis, combined with convergent synthesis based on modern chemical ligation methods for the condensation of unprotected peptide segments, will be described as a path to green synthesis of peptides and their efficient manufacture. Only the most pertinent primary literature is cited.