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New peptide manufacturing method could produce cheaper medicines
Scientists have developed a new method of synthesising peptides which could improve the efficiency of drug manufacturing processes.

Over 70 different peptide drugs are approved for clinical use and used to treat a range of illnesses including diabetes, cancer and HIV, with more drugs currently in development. An increase in the number of available peptide treatments means that peptide manufacturing technology will need to adapt to in order to meet future manufacturing demands.

This new technique developed by scientists at Imperial College London, known as PEPSTAR, provides an efficient way to speed up the process of peptide synthesis without compromising on quality. It has the potential to be scaled-up for commercial use and could be extended to the production of other sequence-defined polymers in a variety of applications.

Solid and liquid challenges
Peptides must be built from an exact sequence of amino acids, so the ability to remove any excess amino acids that are not part of the sequence before adding another is a crucial step in the manufacturing process.

"PEPSTAR is a more flexible platform compared to the classic solid phase method, and it provides more options for further optimisations of the peptide manufacturing process."
Professor Andrew Livingston

Currently, most peptide drugs are manufactured using the solid phase method, which couples amino acids to insoluble solid supports and then washes away any excess amino acids from the support-bound growing peptides after coupling. The main advantage of this method is that it can be easily automated to enable rapid synthesis in a single reactor.

However, the solid phase method is challenging to scale-up. There are “diffusional limitations” in the solid supports, where amino acids need to diffuse towards the interior of the solid resin beads to couple. These limitations can cause incomplete reactions, leading to low Peptide manufacturing purity. Excess reagents have to be used to ‘drive’ the reactions to completion, which makes the process more costly and less efficient.

One way to address these challenges is by using the liquid phase method instead. In this method, the supports that the amino acids are attached to are soluble, and the peptides are all grown by coupling amino acids one after another to the soluble supports in liquid phase. This removes the problem of diffusional limitations so that the purity of the peptides produced is greater, and there is less need for using excess reagents to drive the reactions to completion.

However, the liquid phase method has so far been hampered by slow and complex extraction or precipitation methods. These methods typically require support-bound growing peptides to be transferred between apparatus or isolation via a phase transfer (e.g. liquid to solid) during different cycles of the process. Material and phase transfers make the liquid phase method challenging to scale-up or automate.