Peptide synthesis and flow chemistry

In early 2017, I spent two weeks working off site with a collaborator, New Path Molecular Research, helping to develop what would become Vapourtec’s peptide synthesis platform. Crikey what a project it was, talk about fascinating! The overall concept is deceptively simple, as all good concepts are really; you start with some form of solid support, typically some derivative of a Merryfield resin, attach the first amino acid of your peptide sequence to it, and then just keep adding on the right amino acids until your sequence is finished. Chemically detach the end from the support and hey presto! Your nice and clean peptide is ready to use.

The technical challenge was a little more complex, but flow chemistry is ideal for this procedure; batchwise solid-phase peptide synthesis (SPPS) is, frankly, fiddly. Every amino acid you want to add, you first have to deprotect the terminal amino acid already in the sequence, wash and dry. Add the next amino acid and give it sufficient time to react, wash and dry. Deprotect again, wash and dry and so it goes on until your sequence is finished. Each step can take hours in total, and three or four couplings a day is about the best you can hope for. The advantage that flow brings immediately is that the resin is being constantly washed, merely by virtue of being in flow. So that step of the process is now redundant. Also, in flow we can easily pre-activate our amino acids, usually to an ester, so the coupling is fast; this can be done in batch too, but the activated species must be used quickly, otherwise it can racemise or decompose. In flow we can pre-activate the amino acid quickly and pass it immediately over the deprotected sequence on the resin.

The new platform is complex, it’s probably the most advanced Vapourtec configuration I’ve worked on but with that complexity comes some impressive capability (which can be read about in detail here). Automated liquid handlers let you dial in the sequence you need, and inline spectroscopic and physical measurements allow real-time monitoring of the efficiency of each coupling, and if a coupling hasn’t worked properly? Run it again. As long as the newly added amino acid is not deprotected first, you can only build the sequence that you want.

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Achema – Frankfurt 2018

I love a conference, and Achema really is one of the biggest around! Once every 3 years, specialists from around the world gather to showcase chemical equipment and technology. The most recent took place a couple of weeks ago in Frankfurt, and I was lucky enough to be there with Vapourtec.

Conferences are a fantastic opportunity to meet people in the flow chemistry community. It’s always great to talk to other vendors, catch-up with existing customers and hopefully meet some new ones. I also had the chance to present some of the application work that I have done, which is always an exciting opportunity; I spoke in detail for the first time about Vapourtec’s collaboration with New Path Molecular in using an R-Series with a newly developed reactor that, when combined, makes a platform capable of automated peptide synthesis (which will be featured in an upcoming post). I’m really proud to have been part of this project and how the development of new technology has been able to tackle some of the chemical challenges we faced – a theme I have followed since starting my PhD with self-optimising reactors. The talk was well received and resulted in quite a lot of people visiting me at the stand to discuss the chemistry further, which is nice (my slides are here, if you’re interested).

Unique to this conference, all of the flow chemistry vendors allied together and created the Flow Chemistry Pavilion: a focussed concentration of all of the vendors together. I’ll admit I was a little sceptical to start with, we have competitors and they were in close proximity, but the reality is that it worked very well; people with any interest in flow were coming to the pavilion and because everyone was there, we all saw much higher footfall. It also led to a great feeling of community, as all of the vendors started to direct people to the most appropriate supplier for their application: “Need a scale-up option? You need to go and see so and so, just over there.”  “Inline separation you say? Ah, well that chap there is the expert in that.”

All in all, a thoroughly enjoyable conference.