Andrew J. Wilson
Professor of Organic Chemistry
University of Leeds
Development and Exploitation of Tools to Study Protein-Protein Interactions
A key problem in life-sciences research is to understand protein-protein interactions, PPI, with molecular and temporal resolution. In this presentation we will describe our latest efforts to develop tools to analyse PPIs and map them using photo-activated peptide/protein labelling and cross-linking chemistry.
We have developed a suite of 'tag and transfer' diazirine-based cross-linking reagents. Diazirines are ideal cross-linking groups because upon excitation with UV light, they generate highly reactive carbenes capable of indiscriminate insertion into proximal bonds.
Here we will exemplify the power of these new reagents for structural proteomics analyses. In the second part of the presentation, focusing on the helix mediated NOXA-B/MCL-1 PPI we will describe efforts to develop peptides conjugated to ruthenium (II) (tris)chelates as reagents that can perform photo- activated traceless protein-labelling reactions, a necessary first step in being able to label proteins in live cells without abrogating their normal function.