Robotic synthesis of peptides containing metal-oxide-based amino acids

Abstract

Peptides display a range of important properties, controlled by the intrinsic nature of organic side chains, regarding redox activity, charge density, and structure. Here, we demonstrate a new synthetic approach to insert non-coded amino acids that contain metal oxide groups into a desired peptide sequence with a commercial peptide synthesizer. This approach allowed us to design and isolate a range of highly anionic peptides with various sequences, including the amyloid Aβ17–20, the amphiphilic KFE8, and a bacterial chaperone DnaK substrate. By taking advantage of both the inorganic polyoxometalate-based motif and the peptide sequence, the resultant POM peptides enable significant inhibition of amyloid aggregation, switch a β sheet into a β turn, and enhance binding with the molecular chaperone DnaK. Therefore, we show it is possible to program the robotic synthesis of peptides with functional inorganic amino acids as a generic approach for the design and exploration of next-generation artificial biological-inorganic structures.