Last week Dr Manuel Nuño and Dr Keren Abecassis attended a mini-symposium organised by the British Peptide Society and the Protein & Peptide Science Group of the Royal Society of Chemistry.
This peptide chemistry-focused event was a celebration of the work of Dr Eric Atherton on Fmoc Solid Phase Peptide Synthesis (SPPS). And you couldn’t forget that. Every speaker started their talk with humbled thanks to Dr Atherton, and by reminding the audience that they wouldn’t be presenting their work if it wasn’t for his pioneering work.
Several of the speakers had worked with Dr Atherton throughout his career, including Prof John Wade and 2022 Chemistry Nobel Prize winner Prof Morten Meldal. Dr Atherton was also one of the first scientists to explore peptide synthesis in flow over 40 years ago [1].
For Vapourtec, the event was a fantastic occasion to network with the British peptide community and an opportunity to discuss our most recent advances, and address recurring questions:
1. Why Vapourtec flow?
Our VBFR technology inhibits the movement of resin beads while minimising the reactor volume throughout the whole synthesis. This ensures a unique interaction between the reagents and the static solid support, back mixing is eliminated and reaction by-products are removed. High reaction efficiency is achieved, but more importantly, by constraining both the resin and the direction of the reagent flow, the target peptide is preferred even at substoichiometric conditions. The volume of wash solvent is also minimised. In addition to the chemical advantages, we can access real-time in-line data never seen before at that level of detail: Reactor volume change, which can help detect aggregation events, and quantitative UV spectroscopy.
2. Why heating in SPPS?
Heating has two important benefits: preventing β-sheet structures that can lead to aggregation events and increasing reaction kinetics which can be particularly beneficial for sterically difficult couplings. However, not all heating is the same. Our experience supporting continuous flow applications over the last 20 years has taught us that uniform and constant heating is the key to reproducibility. Hot spots or uncontrolled temperature spikes will cause racemisation and can even lead to loss of the ligand, particularly with chlorotrityl type resins.
Manuel commented: “Attending this symposium has been a great opportunity to showcase our technology for both development and scale-up applications. It was great to find out the peptide community has been following Vapourtec’s developments and was curious to see what our reactors and technology look like.”
Scientists from industry were particularly interested in learning more about the PS-30 pilot scale synthesizer, a platform designed to reduce the development time for new peptide drugs in clinical trials. And as we discussed our plans to launch the Peptide-Builder later in the year, faces lit up with excitement. Peptide chemists are clearly looking forward to this fully automated peptide synthesizer that will allow up to 16 peptide sequences to be queued in the software and synthesised over a weekend!
[1] E. Atherton, E. Brown, R. C. Sheppard, and A. Rosevear, “A physically supported gel polymer for low pressure, continuous flow solid phase reactions. Application to solid phase peptide synthesis,” J. Chem. Soc. Chem. Commun., no. 21, pp. 1151–1152, 1981, doi: 10.1039/C39810001151.
