At Penn State University, monoclonal antibodies -- oftendepicted as "molecular seeing-eye dogs" -- are being bred intopotential pit bull terriers.
Chemistry professor Stephen J. Benkovic has raised an initiallitter of catalytic antibodies that can mutilate and inactivatepeptides and proteins rather than merely track them down.
"With such tailor-made antibodies," Benkovic told BioWorld,one could think, for example, of attacking coat proteins on anAIDS virus, or seizing a small hormonal peptide on its way tobind a receptor, and inhibiting or destroying their biologicalfunction." But he added, "This potential is still totallyconceptual."
Today's issue of Science reports Benkovic's experiment as"Antibody-Catalyzed Rearrangement of the Peptide Bond."
The university has applied for a patent on the process. Itclaims in particular the transition-state analog that the PennState team synthesized as the antigen against which togenerate monoclonals in mice. This captured the intermediateinvolved in the conversion of one amino acid to another at thehigh point in its release of energy, incident to the making orbreaking of chemical bonds. Mimicking this process endowedthe resulting antibody with the ability to fracture the peptide'samide bond, a key sequence of all biological protein structures.
In the Penn State experiment, the antibody broke the amidebond of asparagine and converted this amino acid to another,aspartic acid, via an intermediate, succinamide. As Benkovicexplained, "That was going from A to B."
But he pushed the reaction further, from B to C, through asecond transition state, from the succinamide to aspartic acid."It was the first time this two-step antibody catalysis has beendemonstrated," he said. What's more, he added, the processworks on both L- and D- stereoisomers.
Diane Schloeder, a molecular immunologist at Scripps ResearchInstitute in La Jolla, Calif., generated the murine monoclonalsfor Benkovic, who has a long-standing collaboration in the fieldof catalytic antibodies with the Institute's president, Richard A.Lerner.
Lerner told BioWorld that Penn State's feat demonstrates "oneof the most interesting catalytic antibodies, which not onlybinds but destroys its target."
"Most antibodies," Lerner explained, "bind, but leave it to othermechanisms to do the dirty work. This one acts as a primaryeffector -- trigger and warhead both."
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.