Every now and again I hear the question “which solvent do you recommend for my solid phase peptide synthesis?” Historically, dichloromethane (DCM) was used as a solvent for solid phase synthesis as the kinetics of amino acid activation and amine coupling were much more favorable. However, solubility concerns, particularly for Fmoc-protected amino acids limited the utility of the solvent. Nowadays, DMF and NMP are the two principle solvents for both microwave assisted and room temperature solid phase peptide synthesis. But the question remains, which one is better?
In today’s post, I will compare how the choice of dimethylformamide (DMF) or N-methylpyrolidone (NMP) effects the synthesis of a short yet very hydrophobic peptide.