Our next speakers in the PPSG online seminars series are from Elena De Vita (QMUL) and Yujia Qing (Oxford). Register for a Zoom link by clicking on the registration link.
Dr Elena De Vita - Quen Mary university of London
Title: A covalent inhibition strategy to target Rab27A’s protein-protein interactions
Abstract: Targeted covalent inhibition (TCI) is a resurging drug discovery approach which has proven effective to address previously intractable targets, as demonstrated by the recent breakthrough approval of Sotorasib, the first clinical inhibitor of a mutated KRas. We have used a TCI strategy to target Rab27, a small GTPase that docks to intracellular vesicles and regulates their trafficking by interacting with specific effector proteins via protein-protein interactions (PPIs). Targeting unique cysteines found flanking a critical PPI pocket, we were able to develop the first covalent ligands with on-target activity against Rab27, as shown by chemical proteomics and phenotypic assays.
Dr Yujia Qing - University of Oxford
Title: Dr Towards nanopore proteomics: Enzyme-less single-molecule analysis of full-length proteins
Abstract: Means to sequence DNA and RNA quickly and cheaply have revolutionised biology and medicine. The ability to analyse cellular proteins and their millions of variants would be an advance of comparable importance. Nanopore technology offers single-molecule sensing platforms for ultra-long biopolymers. We aim to leverage the long-read capability of the nanopore approach for full-length protein analysis. Here, we use electroosmosis for the non-enzymatic capture, unfolding and translocation of individual polypeptides of more than 1200 residues by a protein nanopore. By monitoring the ionic current carried by the nanopore, we locate post-translational modifications deep within the polypeptide chains, and thereby lay the groundwork for obtaining inventories of the proteoforms in cells and tissues.
Dr Elena De Vita - Quen Mary university of London
Title: A covalent inhibition strategy to target Rab27A’s protein-protein interactions
Abstract: Targeted covalent inhibition (TCI) is a resurging drug discovery approach which has proven effective to address previously intractable targets, as demonstrated by the recent breakthrough approval of Sotorasib, the first clinical inhibitor of a mutated KRas. We have used a TCI strategy to target Rab27, a small GTPase that docks to intracellular vesicles and regulates their trafficking by interacting with specific effector proteins via protein-protein interactions (PPIs). Targeting unique cysteines found flanking a critical PPI pocket, we were able to develop the first covalent ligands with on-target activity against Rab27, as shown by chemical proteomics and phenotypic assays.
Dr Yujia Qing - University of Oxford
Title: Dr Towards nanopore proteomics: Enzyme-less single-molecule analysis of full-length proteins
Abstract: Means to sequence DNA and RNA quickly and cheaply have revolutionised biology and medicine. The ability to analyse cellular proteins and their millions of variants would be an advance of comparable importance. Nanopore technology offers single-molecule sensing platforms for ultra-long biopolymers. We aim to leverage the long-read capability of the nanopore approach for full-length protein analysis. Here, we use electroosmosis for the non-enzymatic capture, unfolding and translocation of individual polypeptides of more than 1200 residues by a protein nanopore. By monitoring the ionic current carried by the nanopore, we locate post-translational modifications deep within the polypeptide chains, and thereby lay the groundwork for obtaining inventories of the proteoforms in cells and tissues.
