New molecules have been identified that could help to prevent diseases caused by faulty ion channels, such as cystic fibrosis.
Defective ion channels, proteins found in a cell’s membrane, are the underlying cause of many diseases because the transport of chloride ions is impaired.
Although synthetic transporters that can carry chloride through lipid-bilayer membranes have been developed, which could potentially replace the function of faulty channels, they can also carry protons or hydroxide ions, which could disrupt pH homeostasis in the human body.
However, a new study involving an international team of researchers is the first to show anion transporters with a high selectivity for chloride over protons and hydroxide.
Writing in Chem, the researchers said that proton/hydroxide transport is an overlooked side effect of synthetic anion transporters and they synthesised two new molecules to help overcome the issue.
The molecules have high selectivity for carrying chloride ions over protons and hydroxide and one of the compounds enabled chloride transport in real cells without seriously affecting lysosomal pH.
Lead author and PhD student, Xin Wu from the University of Southampton, UK, said: “These new findings represent a paradigm shift for transporter design and provide important clues on how to develop anion transporters for different biomedical applications.
“We showed that different classes of anion transporters can have different behaviour in regulating ion gradients, membrane potential and pH gradients in cells. You need to pick the right molecule to have the desired biological effect for treating a certain disease.”
Professor Phil Gale, head of chemistry at the University of Southampton and the report’s co-author, added: “We demonstrated the possibility to develop molecules to replace the function of chloride channels without disrupting pH homeostasis.
“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.”
Wu X et al. Nonprotonophoric Electrogenic Cl_ Transport Mediated by Valinomycin-like Carriers. Chem 9 June 2016 [abstract]
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