Positively charged peptides can be used to deliver drugs to cells if the correct counterion is used, say researchers.

A 'purely curiosity driven' collaboration between scientists in Switzerland and Japan has led to a simple method to transport peptides across cell walls. Stefan Matile and Naomi Sakai at the University of Geneva and Shiroh Futaki from Kyoto University met at a conference in 2003 and combined their expertise to focus on the phenomenon of cell penetrating peptides (CPPs). The team has discovered how CPPs enter cells and developed a method to use them to deliver peptides into cells.

CPPs are small peptides that contain lots of the amino acid arginine. Arginine has a positively charged side-chain, giving CPPs an overall positive charge. Until now, how arginine-rich peptides enter cells has been a mystery, termed 'arginine magic' by the biological community. The researchers found that the 'magic' is thanks to the counterions, which allow the CPPs to cross the lipid membranes surrounding the cells.

CPPs have attracted a large amount of interest as potential drug delivery agents, said Matile. However, CPP uptake into cells has not always been successful. The scientists have shown that the correct negative counterions can form complexes with CPPs. These complexes can make transient pores through the cell wall to the inside of the cell, where the CPPs are released. 'Once you realise that the counteranions mediate dynamic function, everything seems to make perfect sense,' Matile explained.

Having shown that the right counterion can help CPPs enter cells, the researchers' next step will be to improve the cell targeting of CPPs using specific counterions. Matile believes that there is more to be learnt from counterions. Studying these anions can 'highlight the fundamental importance of chemistry in biology, not only to make new functional molecules but to find rational explanations on the molecular level,' said Matile.

Laura Howes