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In collaboration with Eli Lilly and the University of KwaZulu-Natal, a team in the Department of Chemical Engineering’s Livingston Group have developed PEPSTAR, a “one pot” liquid phase method that is able to isolate growing peptide synthesis using a process called organic solvent nanofiltration (OSN), which filters out any reaction debris and isolates the growing peptides without any phase or material transfers between cycles.

A typical PEPSTAR synthesis cycle involves:

coupling the amino acid to a “nanostar” support;
removing the Fmoc protecting group;
quenching, and
filtering out the reaction debris through a membrane to effect “nanostar sieving”

The key features of the PEPSTAR process (Source: Jet Yeo et. al., Angewandte Chemie)
In their research, the team used the PEPSTAR platform to successfully synthesise a range of short peptides (5-10 amino acids). They found that these peptides had higher purity and could be synthesised at half the cost of standard samples produced using the solid phase method.

A promising future for PEPSTAR
Principal Investigator Professor Andrew Livingston said: “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. This has the potential to drive the cost of peptide drugs down and make them more widely accessible to patients.”

"This novel approach offers not only a new paradigm for peptide synthesis, but is also applicable across the synthesis of other high-precision polymers".

While the method has only been used for shorter peptides so far, researcher Jet Yeo anticipates that making a few changes to the process could allow for very long peptides (chains of more than 20 amino acids) or proteins (chains of more than 50 amino acids) to be produced using PEPSTAR in the future.

This is particularly exciting, because it means that PEPSTAR could be used for synthesis in other processes too. Co-author Jet Yeo explained: “This novel approach offers not only a new paradigm for peptide synthesis, but is also applicable across the synthesis of other high-precision polymers such as oligonucleotides, polyesters, and polyethylene glycols.” These high-precision polymers have applications in many areas, such as genetic testing, forensics and medicine.