Non-enzymatic protein templates amide bond formation and provides catalytic turnover.

The spatial alignment of functional groups is a central aspect of most catalytic processes. Protein scaffolds with their exceptional molecular recognition properties have evolved into powerful biological catalysts. However, the rational design of artificial enzymes starting from non-catalytic protein domains proved challenging. Herein, we report the use of a non-enzymatic protein as template for amide bond formation. Starting from a protein adaptor domain capable of simultaneously binding to two peptide ligands, we designed a catalytic transfer reaction based on the native chemical ligation. This system was used for the selective labelling of a target protein validating its high chemoselectivity and potential as a novel tool for the selective covalent modification of proteins.