A Platform for Chemical Probe Identification and Optimization Facilitating Interrogation of Biological Mechanisms

启用物理科学的方法在研究蛋白质--生物学的主力--方面是极其强大的。蛋白质在细胞中发挥着相当大的功能，使生命成为可能，并相互作用，调节彼此的功能。通过这种方式，蛋白质控制着调节生命的大部分细胞过程，因此，我们必须继续开发能够支持蛋白质功能研究的物理科学方法，以提供改善食品安全的见解，以及诊断和治疗疾病的工具。合成化学探针通过与蛋白质靶标结合发挥作用，可以暂时做到这一点，也可以通过永久连接到它们的靶标来做到这一点。在这两种情况下，“化学蛋白质组学”领域代表了一种方法，通过这种方法，化学探针与其在细胞中的蛋白质靶标相互作用，以了解探针和/或蛋白质在生物学中的作用。化学探针可以是小分子药物、其他生物活性分子，也可以是读出细胞用来控制蛋白质功能的蛋白质相互作用、蛋白质活性或蛋白质修饰的工具。为了进行化学蛋白质组学，有必要识别和量化细胞中蛋白质的变化；这可以使用高分辨率质谱学来实现。质谱仪是一种测量离子质量电荷比的分析技术；它只需要很少的样本量，可以明确地识别和定量细胞中的单个蛋白质，并识别合成化学探针的细胞靶标。这一战略性设备计划将在利兹大学安装一台最先进的质谱仪，使一大批研究人员能够进行化学蛋白质组学研究，开发化学探针并调查与动植物相关的生物过程，包括癌症、痴呆症、心血管疾病和作物胁迫。这将为干预生物过程创造相当大的机会：(A)更好地了解健康细胞；(B)开发新疗法；(C)改善粮食安全。

Enabling physical sciences methods are tremendously powerful in studying proteins - the workhorses of biology. Proteins perform a significant proportion of functions in cells to make life possible and interact with one another to regulate each other's functions. In this way, proteins control the majority of cellular processes that regulate life, therefore it is crucial that we continue to develop enabling physical sciences methods to underpin the study of protein function to deliver insights that improve food security alongside tools to diagnose and treat disease. Synthetic chemical probes function by binding to protein targets and can do so either temporarily, or by linking permanently to their target. In either case, the field of "chemical proteomics" represents the approach by which interaction of a chemical probe with its protein target in cells is used to learn about the role of probe and/or protein in biology. Chemical probes can be small molecule drugs, other biologically active molecules, or tools to read-out the interactions of proteins, protein activity, or protein modifications that the cell uses to control protein function. To carry out chemical proteomics it is necessary to identify and quantify changes to proteins in the cell; this can be achieved using high-resolution mass-spectrometry. Mass-spectrometry is an analytical technique that measures the mass-to-charge ratio of ions; it requires only low sample quantities and can unambiguously identify and quantify individual proteins from cells and identify the cellular targets of synthetic chemical probes. This strategic equipment initiative will install a new state-of-the-art mass-spectrometer at The University of Leeds making chemical proteomics possible for a large group of researchers developing chemical probes and investigating biological processes relevant to animals and plants, including cancer, dementia, cardiovascular disease and crop stress. This will generate considerable opportunities for intervening in biological processes (a) to understand healthy cells better (b) to develop new therapeutics (c) to improve food security.