Identification of New Ligands for Protein Domains Through Reactive Fragment Screening

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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.