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Double ion carriers offer drug lead
14 May 2007
Synthetic molecules that can simultaneously transport two different ions across a membrane could lead to a new class of drugs.
The prodigiosin family of natural products has a variety of therapeutic effects including toxicity to micro-organisms and killing tumour cells. These beneficial activities are linked to the simultaneous transport - known as symport - of hydrogen and chloride ions across a cell membrane. Replicating this co-transport with synthetic molecules opens up the possibility of creating symport based drugs.
Chloride ions (green) fit snugly into the hydrogen bonding pocket of the carrier molecule
Now, a team of researchers led by Phil Gale, at the University of Southampton, UK, and Bradley Smith at the University of Notre Dame, Indiana, US, has managed to do just that. The researchers designed prodigiosin mimics that can efficiently co-transport hydrogen chloride out of vesicles. The team used a pyridine ring modified with two amide groups in the core of the carrier molecule to increase the chloride affinity. The design of the carrier molecule also allowed it to adopt a more organised structure, increasing the transport efficiency.
'Potentially, this line of research could lead to new therapeutic agents' said Gale. 'The future challenge will be to achieve tissue specificity,' he added.
Link to journal article
Conformational control of HCl co-transporter: imidazole functionalised isophthalamide vs. 2,6-dicarboxamidopyridine
Philip A. Gale, Joachim Garric, Mark E. Light, Beth A. McNally and Bradley D. Smith, Chem. Commun., 2007, 1736