Now, a team of chemists at the University of Illinois at Urbana-Champaign, led by professors Steven C. Zimmerman and Kenneth S. Suslick, has developed a way of creating artificial antibodies. The process -- which they describe in the July 25 issue of the journal 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," said Zimmerman, a William H. and Janet Lycan 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 said. "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," said Suslick, also a William H. and Janet Lycan 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 said. "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."
In addition to Zimmerman and Suslick, collaborators on the project were graduate students Michael Wendland and Neal Rakow (both now at 3M) and Ilya Zharov, a postdoctoral research associate at the university's Beckman Institute for Advanced Science and Technology. The National Institutes of Health and the U.S. Army Research Office funded the work.
Journal
Nature