Date: 5 February 2025 | Category: Headline News, News
We report on an exciting collaboration, Vapourtec and the Trant Team from the University of Windsor are working together towards improving the efficiency of solid-phase peptide synthesis (SPPS) by using Fast Flow SPPS.
Led by Professor John Trant, the Trant Team is the largest medicinal chemistry research group in Canada, focusing on synthetic organic chemistry for biological and medical applications.
This partnership aims to enhance the synthesis of peptides and small proteins using sub-stoichiometric amounts of amino acids without compromising purity nor synthesis time.
“The main drive for this collaboration is to deepen the understanding of the kinetics of SPPS. This project is focused on exploring whether it is feasible to use an unnatural amino acid as the limiting reagent in SPPS. Showing the extent of its application is very exciting because it is applied science in action.” Duncan, Founder of Vapourtec commented.
The project
The Trant team has developed a series of unnatural amino acids as building blocks for peptides designed to treat diseases.
The current bottleneck is the synthesis of these novel unnatural amino acids. It takes weeks for a chemist to make them and purify them. If both time and reagent costs are added up, each scaffold could cost in excess of $15,000 per gram of unnatural amino acid.
This bottleneck becomes an issue for the synthesis of peptides containing unnatural amino acids, as reagents are typically used in large excess to achieve high crude purities.
VBFR Technology
Vapourtec’s patented Variable Bed Flow Reactor (VBFR) is an innovative approach to peptide synthesis in continuous flow. The VBFR technology inhibits the movement of resin beads while minimising the reactor volume throughout the whole synthesis, ensuring a unique interaction between the reagents and the static solid support.
Back mixing is eliminated and reaction by-products are removed, achieving high reaction efficiency; but more importantly, by constraining both the resin and the direction of the reagent flow, the target peptide is preferred even at substoichiometric conditions.
Combining the use of the VBFR with uniform heating, reaction kinetics are not only enhanced, but aggregation events, such as β-sheet structure formation, are prevented. These improvements in the synthesis process have, in some cases, eliminated the need for a second purification of the peptide, which is a significant advancement compared to traditional batch synthesis methods.
“I’m a little bit surprised with the improved purity. We would expect the same levels the way we do the batch synthesis. We drive high conversion by using a massive excess of amino acid, and that works quite well”. Ezequiel commented.
Using Vapourtec’s peptide synthesiser; the Peptide-ExplorerLT not only reduced operational costs but also opened new avenues for the Trant team in their work in drug discovery, particularly in immunological and anti-cancer applications.
Future of Fast Flow SPPS
For Professor Trant it is clear that peptides as new drug modalities have come to stay. For peptides to become more mainstream, scientists need to work on:
- Improve cycle efficiency to increase purity and sustainability
- Develop novel unnatural amino acids and new protective groups that can improve synthetic strategies
- Make SPPS less wasteful
With more commercially available building blocks, new chemical strategies and an improved synthetic route, scientists will now access sequences that were difficult to make without coupling fragments.