Selective anion transporters
Philip A. Gale
School of Chemistry (F11), University of Sydney, NSW 2006
Time & Place
Wed, 22 Nov 2017 12:00:00 NZDT in Rutherford Room 531
All are welcome
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 agents1 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.2 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 transporters3 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.4 We have developed the first examples of chloride transporters that show selectivity for chloride transport in the presence of fatty acids.5 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.6
- E.N.W. Howe, N. Busschaert, X. Wu, S.N. Berry, J. Ho, M.E. Light, D.D. Czech, H.A. Klein, J.A. Kitchen and P.A. Gale, J. Am. Chem. Soc., 2016, 138, 8301-8308.
- N. Busschaert, S.-H. Park, K.-H. Baek, Y.P. Choi, J. Park, E.N.W. Howe, J.R. Hiscock, L.E. Karagiannidis, I. Marques, V. Félix, W. Namkung, J.L. Sessler, P.A. Gale and I. Shin, Nature Chem., 2017, 9, 667-675.
- X. Wu, L.W. Judd, E.N.W. Howe, A.M. Withecombe, V. Soto-Cerrato, H. Li, N. Busschaert, H. Valkenier, R. Pérez-Tomás, D.N. Sheppard, Y.-B. Jiang, A.P. Davis and P.A. Gale, Chem, 2016, 1, 127-146.
- X. Wu and P.A. Gale, J. Am. Chem. Soc., 2016, 138, 16508-16514.
- H.J. Clarke, E.N.W. Howe, X. Wu, F. Sommer, M. Yano, M.E. Light, S. Kubik and P.A. Gale, J. Am. Chem. Soc. 2016, 138, 16515-16522.
- Y. Yang, X. Wu, N. Busschaert, H. Furuta and P.A. Gale, Chem. Commun. 2017, 53, 9230-9233.
Philip A. Gale received his BA (Hons) in 1992 and his MA and DPhil in 1995 from the University of Oxford before moving to the University of Texas at Austin where he spent two years as a Fulbright Scholar. In 1997 he returned to the Inorganic Chemistry Laboratory at Oxford as a Royal Society University Research Fellow. He moved to a Lectureship at the University of Southampton in 1999 and was promoted to Senior Lecturer in 2002, Reader in 2005 and to a Personal Chair in Supramolecular Chemistry in 2007. In 2014 he was awarded a Doctor of Science degree by the University of Oxford and in January 2017 he moved to the University of Sydney to take up the position of Professor of Chemistry and from April 2017 Head of the School of Chemistry.
Read more here... http://sydney.edu.au/science/people/philip.gale.php