Development of Novel Chemical Probes for Biological Applications

为了充分了解蛋白质和多肽在疾病中的作用，人们对用特定的标记标记蛋白质和多肽靶标非常感兴趣。由于缺乏以受控方式将这些实体与靶蛋白偶联的方法，此类化学标记的应用受到了阻碍。这项处于化学和生物学交界处的合作努力围绕着通过利用迄今未得到充分利用的反应流形开发新的结合化学来解决上述差距，允许使用光化学产生的反应物种仅标记目标蛋白质中的酸性残基。该项目为能够开发新的试剂以了解蛋白质的功能铺平了道路，这些试剂可以以可预测和选择性的方式与感兴趣的生物分子结合。这项工作的总主题与当前EPSRC投资组合中的一个关键增长领域密切相关，特别是化学生物学。此外，这项提议是对葛兰素史克与斯特拉斯克莱德大学之间正在进行的研究合作的补充，该合作涉及由葛兰素史克资助的、设在葛兰素史克实验室的更广泛的工业博士学生项目。

There is significant interest in tagging protein and peptide targets with a particular label in order to fully understand their role in disease. The application of such chemical tags is hampered by the paucity of methods that are available to conjugate these entities to target proteins in a controlled way. This collaborative effort, which is at the interface of chemistry and biology, centres around addressing the gap outlined above through the development of new conjugation chemistry using a hitherto underexploited reaction manifold, allowing for labelling of only acidic residues in a target protein using a photochemically generated reactive species. This project paves the way towards being able to develop new reagents for understanding protein function that can be combined with a biomolecule of interest in a predictable and selective manner. The general theme of the work is strongly aligned with a key growth area in the current EPSRC portfolio, specifically Chemical Biology. In addition, this proposal complements on-going research collaborations between GSK and the University of Strathclyde involving a wider programme of Industrial PhD students based in the GSK laboratories and funded by GSK.