Postdoctoral Research Associate
Rapid, High-Fidelity Chemical Synthesis of Biologically Active Proteins and Enzymes
The field of biopharmaceuticals is rapidly expanding, requiring new methods for on-demand high-fidelity production of chemically modified proteins. Even after decades of optimization, standard solid-phase peptide synthesis, SPPS, cannot reliably produce peptides containing more than 50 amino acids in length. Larger peptides and proteins are produced by biological techniques, which limits their chemical composition.
Here we report a method that closes the gap between SPPS and biological techniques. Using fully-automated continuous flow-based peptide synthesis, AFPS, we are able to routinely produce long peptides, proteins and protein-like polymers of up to 200 amino acids in a few hours of synthesis time. Complete control of every incorporated amino acid is opening the chemical space to a theoretically unlimited amount of modifications, such as incorporation of functional handles, glycoproteins, post-translational modifications and the synthesis of D-proteins. To validate the general applicability of this new technique, we report the synthesis and biological evaluation of selected examples.