Solvent-Free Peptide Synthesis

Stringing amino acids into a peptide typically takes a large amount of solvent. Chemists in France led by Frédéric Lamaty of the Institut des Biomolécules Max Mousseron, in Montpellier, have now developed the first solvent-free method for making a peptide bond by employing a ball-mill grinder commonly used to process chemicals in paints and pyrotechnics (Angew. Chem. Int. Ed., DOI: 10.1002/anie.200903510). The device consists of a hollow cylinder containing multiple steel balls. When the vessel is loaded with reagents and set to spin, the internal cascade intimately mixes the chemicals so that they react. Lamaty and coworkers used the ball mill to couple urethane-protected α-amino acid N-carboxyanhydride derivatives with α-amino acids, amides, and esters to produce several different dipeptides, including the artificial sweetener aspartame, as well as a tripeptide. Ball-milling offers a greener approach to peptides, the researchers say, particularly as these compounds become more popular as pharmaceuticals.