Identification of New Ligands for Protein Domains Through Reactive Fragment Screening

许多与治疗相关的蛋白质，包括较大受体靶标的结构域，缺乏明确的三维形状。这使得使用已建立的基于结构的方法为这些目标寻找新的线索成为一个特殊的挑战。通过利用在斯特拉斯克莱德开发的能力，了解反应弹头，如腈亚胺物种，该项目的目的是通过一系列生物物理技术，包括SPR，ITC，和本地质谱，使用反应片段筛选方法，找到一系列无序蛋白质的新配体。除此之外，所开发的反应弹头技术可用于开发新的方法来标记蛋白质，以应用于化学生物学。这还可以包括通过开发新的缀合化学来制备抗体药物缀合物的新方法。该项目有可能生成大量的绑定和功能数据，可以使用AI/ML技术进一步利用这些数据来找到最佳线索。

Many proteins of therapeutic relevance, including domains of larger receptor targets, lack a well defined three dimensional shape. This makes finding new leads for these targets a particular challenge using established structure-based methods. Through exploiting capability developed at Strathclyde in understanding reactive warheads such as nitrile imine species, this project aims to find new ligands for a range of disordered proteins using a reactive fragment screening approach via a range of biophysical techniques including, SPR, ITC, and native mass spectrometry. In addition to this the reactive warhead technology developed could be used to develop new approaches to labelling proteins for applications in chemical biology. This could also include new approaches to preparing antibody drug conjugates through development of novel conjugation chemistries. This project has the potential to generate a large volume of binding and functional data which can be further leveraged using AI/ML techniques to find the optimum lead.