Greener Peptide Synthesis: How to Adopt New Solvents in the Wake of DMF Restrictions

The European Commission has adopted a regulation amending Annex XVII of REACH to restrict the solvent N,N-dimethylformamide (DMF) due to its high toxicity on the EU market as of December 12, 2023.

Until now, DMF has been considered the gold standard in solid phase peptide synthesis (SPPS). Multiple alternative, less hazardous and environmentally friendly solvents/solvent mixtures were studied by research groups and companies worldwide to assess their potential in SPPS.

In this application note, we focus on two promising alternatives: N-methyl-2-pyrrolidone (NBP) and a binary mixture of Dimethyl Sulfoxide (DMSO) and Ethyl Acetate (EtOAc). In a series of experiments with different reaction conditions to synthesize three model peptides, we will elucidate the adaptability of the PurePep® Chorus synthesizer to use these solvent alternatives toward a greener synthesis of peptides.

What you will learn about

• Comprehensive study about the effect of solvents DMF, NBP, and DMSO/EtOAc and temperature on crude purities.
• How to switch the process to green solvents on Chorus peptide synthesizers smoothly and quickly.
• Performance of automated peptide synthesis on PurePep Chorus using NBP and DMSO/EtOAc replacing hazardous DMF.
• The effect of induction heating on binary solvent mixtures at elevated temperatures.