Dendrimers Form Artificial Antibodies

Applied Genetics News, August, 2002

Antibody molecules will search out and bind with high affinity a single foreign molecule from a milieu filled with other natural substances. This type of exquisite molecular recognition has long inspired chemists, who for decades have tried to make molecules with similar properties.

A team of chemists at the University of Illinois at Urbana- Champaign (Office of Public Affairs, Swanlund Administration Bldg., 601 East John St., Champaign, IL 61820; Tel: 217/333-5010; Website: www.uiuc.edu), led by Steven C. Zimmerman and Kenneth S. Suslick, has developed a way of creating artificial antibodies. The process, described in the July 25 issue of Nature, is a general approach wherein one molecule imprints its structure within a larger host molecule, in much the same way an object can cast its own shape in plaster of paris.

"This is the first example of molecular imprinting in which a single molecular template is imprinted into a single macromolecule-a highly branched polymer called a dendrimer," says Zimmerman, professor of chemistry at Illinois. "Upon removal of the template, we have a synthetic molecular shell that can bind specifically shaped molecules and reject all others, just like a natural antibody."

The process Zimmerman and Suslick describe is analogous to Linus Pauling's 1940 proposal for how antibodies are formed in response to the presence of an antigen. Although Pauling's mechanism proved to be incorrect, it inspired considerable experimental work, which ultimately led to the modern field of polymer imprinting.

One disadvantage of conventional polymer imprinting is that each "antigen" or template molecule produces an artificial antibody containing all kinds of different binding sites, most of which have poor recognition abilities and are therefore ineffective.

"Using dendrimers for imprinting one molecule against another is much faster and more efficient," Zimmerman says. "And, having a single binding site within a single polymer means we can more easily separate the good imprints from the bad."

To make their molecular molds, the researchers begin by attaching wedge-shaped molecules called "dendrons" to a porphyrin core to create a dendrimer. The flexible dendrimer scaffolding is then cross-linked in a chemical reaction that stitches together the end-groups of the dendrons. Lastly, a hydrolysis reaction chemically clips out the core, leaving a hollow space that can selectively and tightly bind appropriately shaped molecules.

"The technique is similar to the lost wax process used in metal casting," says Suslick, also a professor of chemistry at Illinois. "In essence, we are molding this dendrimer around our template and creating a rigid cast that functions like a molecular lock for a molecular key."

The technique should be applicable to many molecules and a host of molecular recognition tasks. Potential applications include organic catalysts, medical diagnostics, and sensors for various pollutants and chemical warfare agents.

"Right now, we have a conceptual advance," Zimmerman contends. "We've shown there's a new approach that can imprint a single molecule within a single molecule. Ultimately, we envision taking a template, and in a single step growing the scaffolding that can then be linked together to make a rigid mold."