Nonprotonophoric Electrogenic Cl− Transport Mediated by Valinomycin-like Carriers

Xin Wu, Luke W. Judd, Ethan N.W. Howe, Anne M. Withecombe, Vanessa Soto-Cerrato, Hongyu Li, Nathalie Busschaert, Hennie Valkenier, Ricardo Pérez-Tomás, David N. Sheppard, Yun-Bao Jiang, Anthony P. Davis, Philip A. Gale
  • Chem, July 2016, Elsevier
  • DOI: 10.1016/j.chempr.2016.04.002

What is it about?

The movement of ions and molecules through biological membranes is regulated by embedded protein channels, carriers, and pumps. The dysfunction of ion channels is the underlying cause of many diseases, notably cystic fibrosis, in which passive chloride ion transport is impaired. A number of groups are making small molecules that can carry chloride through lipid-bilayer membranes and so potentially replace the function of faulty channels, thereby ameliorating the symptoms of these types of diseases. However, many of these transporters exhibit a side effect of pH-gradient disruption, which can lead to cell death. Herein, we show the first examples of transporters with a high selectivity for chloride over proton and hydroxide, which represents a paradigm shift for transporter design. This is a significant step toward real biomedical application of anion transporters in the battle against cystic fibrosis and other diseases caused by faulty ion channels.

Why is it important?

The key findings in this paper are: Anionophores can function via electrogenic or electroneutral mechanisms Most synthetic anionophores also function as protonophores Proton and hydroxide transport are two mechanisms for protonophoric activity Anion encapsulation confers selectivity for chloride over protons/hydroxide

Perspectives

Professor Philip Gale
University of Southampton

This paper is significant because it describes new assays for measuring the selectivity of transmembrane transporters for chloride (or other anions) over protons or hydroxide. It also points the way forward to design chloride selective transporters that may be useful in the future in the treatment of cystic fibrosis.

Read Publication

http://dx.doi.org/10.1016/j.chempr.2016.04.002

The following have contributed to this page: Professor Philip Gale