A Combined and Automated High Throughput Parallel Peptide Synthesis Platform.

我们希望为巴斯大学的生化设施增加一项重要的尖端平台技术，即制造和测试大量非常小的蛋白质（即肽）的能力。全球多肽治疗市场价值360亿美元，预计到2027年将达到620亿美元。人们普遍认为，蛋白质之间的相互作用对生命至关重要，当蛋白质出错时，阻止这种相互作用的能力在药物发现和化学生物学中变得越来越重要。因此，蛋白质-蛋白质相互作用被认为是非常重要的药物靶点，但由于小分子或较大的生物制剂难以接近，因此历史上一直被认为是“不可药物的”。多肽占据了一个方便的中间地带，在这一领域的研究开发了许多令人兴奋和创新的方法来识别基于多肽的抑制剂以及与疾病有关的蛋白质的工具和探针。因此，在单一平台内制造和测试大量肽的能力提供了特别强大的能力。此外，我们将围绕跨学科团队组成的临界质量，在MRC战略优先领域开展新的研究，并提高现有和新员工的培训潜力，包括研究技术专业人员和MRC DTP学生。我们寻求的单一技术平台在英国是独一无二的，由高通量低规模（数千个肽）全自动平行肽合成器以及更高数量的肽的规模化合成（1-24个肽）组成。这具有无与伦比的灵活性，可对多达2400个多肽进行高通量筛选，并将通过能够并行制造/测试许多多肽来识别那些值得大规模进一步研究的多肽，从而显着提高英国的能力。有许多计划中的研究将充分利用高通量平行肽合成和规模化单肽合成带来的新能力。这些研究也可能鼓励巴斯大学、GW4以及国内和国际范围内广泛的跨学科参与。绝大多数设备用户群将在UKRI-MRC和生物医学科学领域进行研究。重要的是，该提案还包括对已建立和早期职业研究人员以及研究技术人员的培训和支持计划，并包括安装，用户预订，正在进行的平台服务的成本回收，以及旨在鼓励广泛用户吸收的培训/研讨会活动。同时将许多不同的科学家聚集在一起进行跨学科合作。

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 remitImportantly, 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.