Antibacterial agents which act on the plasma membrane structure

6 Antibacterial agents which act on the plasma membrane structure 

The peptides valinomycin (Fig. 10.64) and gramicidin A (Fig. 10.67) both act as ion conducting antibiotics and allow the uncontrolled movement of ions across the cell membrane. Unfortunately, both these agents show no selective toxicity for bacterial over mammalian cells and are therefore useless as therapeutic agents. Their mechanism of action is interesting nevertheless. 

Valinomycin is a cyclic structure containing three molecules of L-valine, three molecules of D-valine, three molecules of L-lactic acid, and three molecules of D-hydroxyisovalerate. These four components are linked in an ordered fashion such that there is an alternating sequence of ester and amide Unking bonds around the cyclic structure. This is achieved by the presence of a lactic or hydroxyvaleric acid unit between each of the six vahne units. Further ordering can be observed by noting that the L and D portions of valine alternate around the cycle, as do the lactate and hydroxyisovalerate units. 

Valinomycin acts as an ion carrier and in some ways could be looked upon as an inverted detergent. Since it is cyclic, it forms a doughnut-type structure where the polar carbonyl oxygens of the ester and amide groups face inside, while the hydro-phobic side-chains of the valine and hydroxyisovalerate units point outwards. This is clearly favoured since the hydrophobic side-chains can interact via van der Waals forces with the fatty Upid interior of the cell membrane, while the polar hydrophilic 

This hydrophilic centre is large enough to accommodate an ion and it is found that a naked potassium ion (i.e. no surrounding water molecules) fits the space and is complexed by the amide carboxyl groups (Fig. 10.65). 

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