A Combined and Automated High Throughput Parallel Peptide Synthesis Platform.

We wish to add an important cutting-edge platform technology to the University of Bath's Biochemical facilities - the ability to make and test large numbers of very small proteins known as peptides. The global peptide therapeutic market is valued at $36B USD, and is expected to reach $62B by 2027. Interactions between proteins is well recognised as being essential for life, and the ability to block such interactions when proteins go wrong is becoming increasingly important in drug discovery and chemical biology. Protein-protein interactions are therefore recognised as very important drug targets, but have been historically considered 'undruggable' owing to their inaccessibility to small molecules or larger biologics. Peptides occupy a convenient middle ground, with research in this area developing many exciting and innovative approaches to identify peptide-based inhibitors as well as tools and probes of proteins involved in disease. Consequently, the ability to both make and test large numbers of peptides within a single platform provides a particularly powerful capability.

In addition, we will enable new research in MRC strategic priority areas based around critical mass composed of interdisciplinary teams, and enhance the training potential of both existing and new staff, including research technician professionals, and MRC DTP students. The single technology platform we seek is unique within the UK and consists of a high-throughput low-scale (thousands of peptides) fully automated parallel peptide synthesiser coupled with upscaled synthesis (1-24 peptides) of peptides in much higher amounts. This features unmatched flexibility for high-throughput screening of up to 2400 peptides, and will significantly enhance UK capability by being able to make/test many peptides in parallel to identify those worthy of further study at large scale.

There are many planned studies which will take full advantage of the new capabilities that high throughput parallel peptide synthesis and upscaled single synthesis brings. These studies are also likely to encourage broad interdisciplinary engagement within Bath, the GW4, as well as nationally and internationally. The vast majority of the equipment userbase will be undertaking research within the UKRI-MRC and biomedical science remit

Importantly, this proposal also includes a programme of training and support for both established and early career researchers, as well as research technician professionals, and includes installation, user booking, cost recovery for ongoing platform servicing, and training / workshop events designed to encourage broad user uptake, while bringing many different scientists together for interdisciplinary collaborations.

We seek a single technology platform comprising of a high-throughput low-scale (1-15 umol - thousands of peptides) fully automated parallel peptide synthesiser (CEM, Multipep2) coupled with upscaled synthesis (0.1-5 mmol - 1-24 peptides) of peptides (CEM, liberty Prime 2.0). The first is a state-of-the-art synthesiser featuring unmatched flexibility for high-throughput screening of hundreds of peptides via plates/columns (<384 peptides), or cellulose membrane formats (for peptide microarrays (<2400 peptides; SPOT Synthesis = 2400 peptides on four cellulose membranes, CelluSpots = 768 peptides on a dissolvable cellulose support for spotting on many identical slides). It will significantly enhance capability by synthesizing/screening many peptides (100s-2400) in parallel to identify those worthy of further study at large scale. Launched in Q2 2022, the second platform component will be used in conjunction with the first (but not physically linked) to allow a handful of 'lead' peptides to be upscaled to enable further in-depth characterisation and assessment. There is no MP2/LP2 platform in the UK, and in particular no capability in the SW for parallel synthesis of 1000's of peptides. This award will therefore provide a much-needed capability and will benefit UK bioscience in general by providing a significant advantage in expediting the peptide design process, results, and outputs. It will support a broad, interdisciplinary research community within the University of Bath and our collaborator institutions/organisations.