Sustainable Approaches in Solid-phase Peptide Synthesis (SPPS)

Solid-phase peptide synthesis (SPPS) is a ubiquitous methodology for making peptides from R&D to manufacturing plant, not least in the context of using peptides and peptidometics as pharmaceuticals. Nevertheless, SPPS has long been plagued by its reliance on large amounts of hazardous materials such as dimethylformamide as the solvent and trifluoroacetic acid as the cleavage reagent. Consequently, with methods for producing peptides in a sustainable manner being in high demand, numerous reports covering various aspects of SPPS greening have appeared in recent years. In this chapter, an integrated overview of state-of-the-art methods in the sustainable SPPS field is presented, highlighting advances within the entire SPPS workflow from starting materials to amino acid coupling cycle to cleaving the peptide off the polymer support. Greener methods for the assembly of complex peptides and waste minimization tactics are also delineated, together with a discussion of adoption in practice, scale-up, procurement, costs and intellectual property as key considerations for attaining truly sustainable SPPS. Finally, a perspective on future directions towards elevating SPPS as a versatile, sustainable peptide synthesis platform is provided.