Development of a sustainable approach to the manufacture of peptide and protein derivatives

Lead Research Organisation: University of Strathclyde
Department Name: Pure and Applied Chemistry

Abstract

Significant efforts have been invested in recent years by the pharmaceutical industry in the development and manufacture of bioactive peptides and protein derivatives for the treatment of diseases of societal need. The global peptide therapeutics market size was valued at US$22 Billion in 2017, and is anticipated to grow by 9.1% over the forecast period 2018 - 2026. Accordingly, there is a clear need for innovative strategies to enable the efficient and sustainable manufacture of this growing class of medicine in order to maintain pace with a rapidly expanding market.
This industry-facing, collaborative studentship proposal aims to address the major issues associated with the production of peptide and protein derivatives, particularly with regard to sustainability. Working with the world's leading instrument provider in the area, and capitalising on synthetic chemistry expertise at Strathclyde, we aim to establish a new platform for more cost-effective and environmentally friendly peptide synthesis in a fully automated fashion, thus helping to futureproof the supply chain of an expanding class of valuable medicinal products.
As stated above, synthetic peptide and protein derivatives are now a mainstay in the treatment and management of a range of diseases. Our current armamentarium of synthetic chemistry technology for peptide manufacture was developed over 50 years ago, and has not kept pace with developments in other areas of synthesis. The most acute issue with our current approaches is their exceedingly poor environmental impact. Peptide and protein medicines can be thought of as consisting of 'building blocks' which can be fused together using an activating agent (a 'molecular glue') forming a so-called amide bond, the basic repeat unit of these molecules. Standard practice is to utilise substantially more of the building blocks and activating agents than is otherwise desirable in order to be certain of preparing the target products in good yield. This necessarily results in an excessive amount of waste, with concomitant impact on both the environmental and economic credentials of the process. This situation is exacerbated by the use of a large volume of solvents which are themselves detrimental to the environment. Overall, a step change is needed in our current manufacturing capabilities to address both the environmental and financial considerations outlined above.
In the current study, we aim to capitalise on expertise developed in the PI's laboratory towards enabling a new and sustainable approach to peptide synthesis. Initial results have shown how it is possible forge the key amide bond which constitutes the peptide backbone in a catalytic manner - that is to say it can be done without using excessive amounts of building blocks and activating agents, thus negating the deleterious impact of the progenitor processes. In addition to this, we have established capability in applying replacement solvents to the key amide bond forming process required for assembly of the target molecule class. These successor solvent systems are derived from sustainable feedstocks (e.g. from sugar beet) and thus do not have the toxicological and environmental issues that will in the future hamper the continued application of the currently available solvent systems. We aim to leverage these two nascent areas of research in collaboration with the instrument technology of Gyros PTI, to design, develop and implement a fully automated approach to the manufacture of important peptide and protein medicines. Although not without a degree of challenge and adventure, combining catalytic chemistry, sustainability and automated synthesis into a single production platform will then represent an innovative and powerful approach to peptide synthesis. Against the background of ever tightening government and regulatory focus, this collaboration will thus help secure our manufacturing capability for this important class of medicine well into the future.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/R513349/1 01/10/2018 30/09/2023
2270409 Studentship EP/R513349/1 01/10/2019 31/03/2023 Jenna Marie Mowat