Ionic liquids and proteases: a clean alliance for semisynthesis

Herein we present the first report on protease-catalysed ligation of cleavage-sensitive peptide and protein fragments in ionic-liquid-containing solvent systems. By applying the newly established MMIM]Me2PO4]/buffer mixture as a reaction medium, significant advantages over purely aqueous or conventional organic solvent-containing media could be identified, including in particular the use of active wild-type proteases as biocatalysts, the suppression of any competitive proteolytic side reactions, the high turnover rates compared to classical organic solvents and the high stability of chemically labile reactants.