Antibody mimics rival the real thing.

Custom-tailored by the immune system to identify and nab specific chemical invaders, antibodies are masters of molecular recognition. Scientists often use them to target a substance within a mixture and measure the amount present, Now. a group of European researchers report they can make artificial antibodies that match the real thing when it comes to detecting minute quantities of two drugs in blood serum.

The researchers built their synthetic antibodies out of polymers, using a technique called molecular imprinting to construct a cast around a target molecule. Because these mimics are robust. reusable. and inexpensive to produce. They may one day replace antibodies harvested from laboratory animals for use in diagnostic tests. "Molecufar imprints may be made against a great number of organic molecules, for example, drugs, hormones, and toxins;' Klaus Mosbach of the University of Lund in Sweden and his colleagues write in the Feb. 18 NATURE. "This technique may have many applications."

The team made antibody mimics against two chemically unrelated drugs, the asthma medication theophylline and a tranquilizer called diazepam. They used a "cocktail" approach, Mosbach says, adding simple organic chemicals called monomers that interact with the "print" molecule in a variety of ways. For instance, methacrylic acid linked up in repeating units to form a polymer cage around the drug molecule, while a chemical cross-linker called ethylene glycol dimethacrylate strengthened the cage. After removing the drug molecule, the researchers had a rigid, insoluble polymer imprinted with the exact shape of the drug, like a handprint set in concrete.

The group found that the mimics showed the same specificity as their antibody counterparts. The synthetic antibody for theophylline invited into its folds only one of the eight structurally related drugs and metabolites tested. The synthetic antibody for diazepam was tricked by several compounds, just as real antibodies are.

The proof came, however, when the researchers used the antibody mimics to determine the amount o! drug in serum samples from 32 patients. The team compared the results with those obtained through a technique using real antibodies, called enzyme-multiplied immunoassay technique (EMIT). The two methods showed complete agreement, Mosbach's group reports,

This is the first demonstration that such antibody mimics can perform as well as real antibodies in a practical application, says Frances H, Arnold of the California Institute of Technology in Pasadena. "This is quite an exciting paper that clearly shows the potential for these imprinted molecules."

At present, imprinted polymers need organic solvents around them in order to work, which makes them more cumbersome to use in biomedical assays than water-loving antibodies. However. Mosbach says, "It's only a matter of a year or so before the molecular imprint methods will be as good as, if not better than, current immunoassay techniques."