Antibacterial polymers designed to distinguish between bacteria and human cells
US biochemists have discovered a highly effective antibacterial polymer, spurring the search for new antibiotics. The polymer kills bacteria by puncturing their cell membranes and, unlike previously studied polymers, can distinguish between bacterial and human cells.
Several synthetic polymers with antibacterial activity are known, including poly(vinyl pyridine), poly(vinyl alcohol) and polyacrylate. They are all amphiphilic - possessing hydrophilic and hydrophobic ends - and work in the same way. The hydrophobic end naturally embeds itself into cell membranes, causing the contents to leak out.
Unfortunately, the polymers so far studied are just as likely to embed themselves into human cells as bacterial ones, which has limited their development as antibacterials.
Natural host defence peptides, which work in a similar way, get around this problem by having cationic side chains that are preferentially attracted to the dense population of negatively-charged lipids on bacterial cell surfaces. Kenichi Kuroda and William DeGrado from the University of Pennsylvania, Philadelphia, developed amphi-philic polymers that possess similar cationic compounds.
They carried out radical copolymerisations of N-(tert-butoxycarbonyl)amino-ethyl methacrylate and butyl methacrylate to produce polymethacrylate, which they then treated with trifluoroacetic acid to add a cationic compound. They also conducted the copolymerisation in the presence of methyl 3-mercaptopropionate, which acted as a chain transfer agent and allowed the researchers to produce polymers with a range of different molecular weights.
The researchers tested these polymers against cells from the bacterium Escherichia coli and human red blood cells and found that the polymethacrylate compound with the smallest molecular weight (1300-1900) possessed the best combination of properties. It killed bacterial cells at a level comparable with melittin, the main toxin of bee venom, but was much less toxic to human cells.
Kuroda and DeGrado are now working to improve the polymers’ potency, selectivity and versatility. ’We seem to be making progress on all fronts,’ said DeGrado, ’and are looking into copolymers as well as surface derivatives.’
The researchers have licensed the rights to commercialise these polymers to a new company called PolyMedix.
K Kuroda and W F DeGrado, J. Am. Chem. Soc., 2005, 127, 4128
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