Abstract

Flow-based Methods for Chemical Peptide and Protein Synthesis

Nina Hartrampf, Assistant Professor, University of Zurich

The field of biopharmaceuticals is rapidly expanding, requiring new methods for the on-demand production of chemically modified peptides and proteins. This chemical synthesis involves the iterative formation of amide bonds and requires high yields for efficient incorporation of each individual amino acid. Solid-phase peptide synthesis (SPPS) has been a standard method for chemical peptide and protein production for the past 60 years, but its outcome can be highly dependent on the peptide sequence synthesized. One issue that often arises is the aggregation of growing peptide chains on the solid support, which can lead to incomplete couplings ("difficult sequences”), and this effect generally correlates with low synthesis yields. Previous research into this sequence-dependent phenomenon was limited by the lack of high-throughput analytical methods, thus impeding systematic analysis.

As opposed to batch-SPPS, flow-SPPS not only accomplishes rapid synthesis of tailored peptides and proteins but also enables the collection of in-line analytical data that gives new insights into sequence-dependent events such as aggregation. In this presentation, various parameters affecting aggregation will be analyzed, and the development of new computational methods, technological solutions, and synthetic tools to reduce the sequence dependence in SPPS will be disclosed.