Final Report Summary - RUPPIIS (Ruthenium Based Protein-Protein Interaction Inhibitor’s) The goal of this project was to design, synthesis and study (a) protein recognition properties and (b) cellular uptake and localisation behaviour of highly functionalised ruthenium (II) tris bipyridine complexes. The study was to build on established synthetic methods for synthesis (Chem. Eur J. 2010, 16, 100, Chem. Commun., 2011, 559) demonstrable selective high affinity binding to proteins surfaces in particular cytochrome c (Chem. Eur J. 2010, 16, 100, Chem. Commun., 2011, 559) and efficient cellular uptake into HEK 293 cells (Bioorg. Med. Chem. Lett., 2012, 22, 985).In this project the original complexes were resynthesized together with several additional complexes. The majority of subsequent studies focused on cellular uptake of the complexes. Several compounds (including from the original set) were shown to be taken up into an array of different cell types and localise to a range of organelles. Moreover several of the compounds were also shown to exert a cytotoxic effect – preliminary analyses suggests that this is through an apoptotic mechanism. This results further highlight the potential use of highly functionalised ruthenium (II) tris bipyridine complexes as cell permeable inhibitors of protein-protein interactions and open up opportunities for their further use as imaging probes for diagnosis in future. The potential socio-economic significance of this research therefore lies squarely within the life-sciences and health domains. Specifically protein-protein interactions control all biological processes and are central to healthy/disease biology; therefore the availability of small molecule modulators as chemical probes represents a critical step along the pathway to understanding which proteins are relevant to disease and on the drug discovery pathway. For further literature on the topic of protein-protein interactions relevant to this fellowship and other ongoing and related activity taking place within the Host Laboratory see: http://www.chem.leeds.ac.uk/andrew-wilson/wilson-group.html Prof Andy WilsonDeputy Director, Astbury Centre for Structural Molecular BiologyRoom G.15School of ChemistryUniversity of LeedsWoodhouse LaneLeeds LS2 9JTUnited KingdomA.J.Wilson@leeds.ac.uk Office +44 (0)113 3431409Lab +44 (0)113 3436549 or 3436564Fax +44 (0)113 3436565
