The take home message from Andrew Kennedy’s presentation was clear: solid-phase peptide synthesis (SPPS) uses too much solvent and too many reagents. Overreliance on these toxic chemicals lead to hazardous waste which has a negative impact on the planet and is expensive to dispose of. In turn, this also makes peptides more costly to produce.
This presentation outlines AmbioPharm’s solution for peptide synthesis. They wanted to introduce an approach that would simultaneously reduce environmental impact, allow for scalable production, and optimise techniques.
The solution presented by Kennedy was tag-assisted liquid-phase peptide synthesis (LPPS), which combines the benefits of solid-phase and liquid-phase synthesis. It uses a tag which is attached to the growing peptide chain and soluble in certain solutions; this allows for complete reactions in solution. To access the benefits of SPPS, the solvent is switched so that the tag becomes insoluble, precipitating out the product and enabling efficient purification.
A key part of this solution is the Cyclover tag, so-named for its Cyanuric core and four leaf-like alkyl chains. The tag is designed to improve the solubility and efficiency of the synthesis process, allowing for reduced reagent usage and better scalability.
Then Kennedy outlined a comparison of conventional SPPS versus tag-assisted LPPS. Of the two methods compared, tag-assisted LPPS improved crude purity by 10% over conventional SPPS. Kennedy added that there are also opportunities to improve figure more by optimising each precipitation even further. Furthermore, yields can be improved by enhancing the precipitation conditions as well.
Using fewer and greener solvents produced a 30% reduction in consumption suitable for scale up. Manufacturers can efficiently scale up their production while maintaining a high quality and high yield. AmbioPharm’s technology doesn’t require any specialised equipment; if a manufacturer already has the tools to carry out SPPS, they will have what’s required to switch to tag-assisted LPPS.
