WEP 2020 - Credited events catalogue WEP 2020 - Credited events catalogue-11.27 | Page 41

41 EVENT FORMAT Lecture 2020 Januar y 12-2 3 Selective Anion Transport 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 aniono- phores 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 selectivi- ty 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 trans- port in the presence of fatty acids. Using the new assays we have developed, we have shown 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. SPEAKER Philip Gale CREDITS 1 Professor of Chemistry and Head of School at the University of Sydney DESCRIPTION