@misc{9237196,
  abstract     = {{Therapeutic peptides are a fast-increasing segment in the pharmaceutical industry, and GLP-1 analogues stood for two out of the three most sold drugs last year, 2025. The most common production method of peptides is based on Merrifield’s discovery of solid-phase peptide synthesis (SPPS), which uses large volumes of hazardous chemicals like N,N-dimethylformamide (DMF), piperidine, and trifluoracetic acid (TFA). With increasing market demand for peptide-based drugs and more stringent regulations on hazardous chemicals, green commercial production methods are needed. Current research has proposed several alternatives using different protecting groups (PGs) for amino acids and a cosolvent in aqueous solid-phase synthesis (ASPPS), but none have been adopted by industry.

In this report, an investigation has been conducted into the feasibility of performing ASPPS on a model pentapeptide, Leu-enkephalin amide (Tyr-Gly-Gly-Phe-Leu-NH2), using water as the solvent and a hydrophobic αN-terminal PG with increased compatibility with ASPPS, in order to minimize side reactions. The αN-terminal protected amino acids used in the peptide synthesis were also synthesized within the project using greener organic solvents. An investigation of suitable coupling reagents, additives, and conditions was done by optimization of a glycine and leucine coupling, which determined the conditions for the final model peptide synthesis. In the preparatory work, protecting-group removal and sufficient washing procedures were evaluated. The result showed that a water-based synthesis was possible, including all steps, PG-removal, coupling, and cleavage.}},
  author       = {{Wahlqvist, Linnea}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Expanding the reach of aqueous solid-phase peptide synthesis (ASPPS) for linear peptides}},
  year         = {{2026}},
}