Identification of New Ligands for Protein Domains Through Reactive Fragment Screening

许多与治疗相关的蛋白质，包括较大受体靶点的结构域，缺乏明确的三维形状。这使得使用现有的基于结构的方法为这些目标寻找新的线索成为一项特别的挑战。通过利用Strathclyde在理解丁腈亚胺等反应性弹头方面开发的能力，该项目旨在通过一系列生物物理技术（包括SPR、ITC和天然质谱），使用反应性片段筛选方法，为一系列无序蛋白质找到新的配体。除此之外，开发的反应弹头技术可用于开发用于化学生物学应用的标记蛋白质的新方法。这也可能包括通过开发新的偶联化学来制备抗体药物偶联物的新方法。该项目有可能产生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的线索。

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.