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Pores for thought
02 May 2007
Researchers in Switzerland have made artificial membrane pores that can recognise nucleotides.
Pores in cell membranes are channel-like structures, made from proteins, which allow specific molecules to pass into and out of the cell. These pores can also act as sensors, such as those found in taste receptor cells in the human tongue. Natural sensors like these usually rely on ion-pairing interactions to recognise different molecules.
But the synthetic pore, made by Stefan Matile and colleagues at the University of Geneva, uses a different kind of interaction altogether. Matile's pore is made from rigid rods functionalised with pentapeptides, which self-assemble into a barrel structure, just like that of a natural pore. The pentapeptides are themselves functionalised with electron-poor naphthalenediimide molecules. A pair of these electron-poor molecules can act as a clamp, sandwiching an electron-rich analyte such as a nucleotide (a sub-unit of DNA).
The rigid backbone (black) has electron-poor clamps (blue) attached, which can recognise electron-rich analytes (red)
'The pores are bioinspired, but it is wonderful to achieve this small victory over nature in utilising this kind of interaction,' said Matile. 'It may even give us access to new analytes.'
Jean-Marie Lehn, an expert in molecular recognition from Louis Pasteur University, Strasbourg, France, said, 'this work will be very important in understanding how natural pores work, and for designing new types of sensor based on this technology.'
Matile says there are many potential applications for this kind of system, which could lead to diagnostic sensors for cholesterol, inhibitor screens for drug discovery, or even a synthetic tongue that could 'taste' the difference between sweet, sour and umami. 'The next step is to convince potential investors that this is a viable proposition,' he said.
The synthesis of the pore is not easy, but Matile believes the effort pays off; the high activity of these sensors means that hundreds of thousands of assays can be performed using only milligram quantities of pores. 'Potentially, all that is required in order to realise new applications is the appropriate functionalisation of the pentapeptide with the right type of clamp,' said Matile.
Link to journal article
Synthetic pores with sticky -clamps
Hiroyuki Tanaka, Guillaume Bollot, Jiri Mareda, Svetlana Litvinchuk, Duy-Hien Tran, Naomi Sakai and Stefan Matile, Org. Biomol. Chem., 2007, 5, 1369