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Two heads are better than one
27 November 2006
A doubled-up drug could be the answer to superbugs.
Hirokazu Arimoto from Tohoku University, Japan, and his colleagues have prepared a covalently-linked dimer of the antibiotic vancomycin. They found that the double antibiotic was over twice as effective as the single form.
Vancomycin dimers are more effective against bacteria than the single form.
Multidrug-resistant pathogens are of great concern to the medical community. The emergence of vancomycin-resistant bacteria is a particular worry, asserted Arimoto, because vancomycin is the treatment of last resort for multi-resistant Gram-positive bacteria. The concept that connecting two drug molecules plays an important role in their antibacterial effects prompted Arimoto to design his dimers.
The antibacterial activity of the dimers was evaluated using sets of susceptible bacteria and resistant bacteria. The synthetic dimers were found to be effective against a range of resistant strains and showed no toxicity in in vivo tests.
Arimoto believes that the dimers interact directly with the enzymes regulating the late stages of cell wall synthesis, whereas the single molecule has been shown to interact with the enzyme substrates. Further biochemical studies are planned to test these ideas, Arimoto said.
Synthesis of rigidly-linked vancomycin dimers and their in vivo efficacy against resistant bacteria
J Lu, O Yoshida, S Hayashi and H Arimoto, Chem. Commun., 2006,