Where: Building 9 Lecture hall 1
Credit: 1
Description
Lecture by Philip Gale, Professor of Chemistry and Head of School at the University of Sydney.
ABOUT THIS LECTURE
Synthetic transmembrane anion transporters (anionophores) have potential as tools for biomedical research and as therapeutic agents for diseases associated with anion channel dysfunction such as cystic fibrosis (CF). However, the issue of potential H+ or OH- transport by anionophores has received little attention and proven Cl--selective anionophores that do not facilitate the transport of H+ or OH- transport are currently unavailable. HCl co-transport may be useful in the development of anti-cancer agents as proton transport processes have been linked to toxicity. For example, we have recently shown that pH dissipation within cells triggered by a squaramide-based transporter can disrupt autophagy. However, other applications, such as the development of channel replacement therapies for CF require selective transport. We have developed new assays to measure the chloride vs. proton transport selectivity of small-molecule anion transporters and shown that proton transport may be facilitated by receptor deprotonation (weak acid protonophore mechanism) or by facilitating the transport of carboxylate fatty acid head groups through membranes. We have developed the first examples of chloride transporters that show selectivity for chloride transport in the presence of fatty acids. Using the new assays we have developed, we have demonstrated the limitations of the chloride/nitrate exchange assay used by many groups over the years to measure chloride transport and determined EC50 values for sulfate transport for the first time.
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Philip Gale
Philip Gale is a Professor of Chemistry and Head of School at the University of Sydney. His research interests include all aspects of the supramolecular chemistry of anions but in particular their transmembrane transport. He obtained his Ph.D. from the University of Oxford. He then joined Prof. Jonathan Sessler’s group at the University of Texas at Austin as Fulbright Scholar. He returned to the UK to a Royal Society University Research Fellowship in 1997 moving to a lectureship at the University of Southampton in 1999. He was promoted to Professor of Supramolecular Chemistry in 2007 and served as Head of the School of Chemistry between 2010 and 2016.
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