Glycerol-based dipolar aprotic solvents for more efficient and sustainable peptide synthesis and beyond

Abstract: Therapeutic peptides are booming because they are potent, biodegradable and safer. But their synthesis is not. Every kg of peptide needs on average 6'000 kg of single use N,N-Dimethylformamide (DMF), a reprotoxic and fossil-based synthesis solvent. With the entry of ton scale peptides (mainly driven by GLP-1 agonists such as Ozempic), that means DMF consumption increase with millions of liters. This is becoming untenable as DMF exposure limits tighten, and peptide demand is growing at double digit rates. Together, that's incentive to change, but unntil today, there just has not been a greener and high-performing drop-in alternative. We created a new platform of bio-glycerol based solvents which are stable, safe, cost-competitive and outperform DMF in Solid-phase peptide synthesis, the main route for production of medium-to-long peptides. In addition, we are able to scale down amino acids equivalents excess by 90%, while maintaining performance, which has larger green chemistry and financial implications. With our new platform of dipolar aprotic solvents, we want to tackle the major and growing DMF - sustainability challenge in the peptide field, and by expansion in the broader chemical industry.