Many drug molecules exist in mirror-image versions. Often, only one form carries out the intended medical mission?and sometimes the other causes side effects. Now, a new high-tech filter might make it easier to separate mixes into their mirror-image components.
To make the filter, researchers from Florida and Finland created a thin alumina membrane with 35-nanometer-wide pores and grew hollow silica nanotubes inside the holes. That done, the scientists attached antibody fragments to the inside wall of each nanotube.
The Finnish researchers had made these antibody fragments to specifically latch on to only one mirror-image form, or enantiomer, of a test molecule. It’s the first time that anyone has incorporated antibodies in such a filter, says team member David Mitchell of the University of Florida in Gainesville.
When the researchers placed the membrane between one solution containing both enantiomers and another solution with neither, they found that twice as much of the antibody-binding enantiomer passed through the membrane. The antibodies eased the transit of their associated enantiomer. When the researchers used membranes with only 20-nm pores, the molecules passed through them more slowly but with even better selectivity: The ratio of the desired to undesired enantiomer crossing the filter was 4.5 to 1. By using several membranes in series, the selectivity could be increased much further, Mitchell proposes.
He and his coworkers from the University of Florida and VTT Biotechnology in Espoo, Finland, describe their work in the June 21 Science.
The new membrane “has the potential to change the way drugs are manufactured,” comments Reginald M. Penner of the University of California, Irvine.
Previously, membranes were of limited use because they’ve been unable to separate a particular molecule from a mixture with enough specificity, says Timothy J. Ward of Millsaps College in Jackson, Miss. The addition of antibodies to membranes could solve that problem, he says, adding that the new filter has tremendous commercial potential.
However, some engineering hurdles remain, such as scaling up the new membrane to an industrially useful size, Ward says.
Because it’s possible to create antibodies for an enormous range of molecules, antibody-laden membranes could do a host of molecule-sorting jobs beyond separating enantiomers, says Mitchell.
