This technology represents the first time catalytic antibodies have been used in human therapy.
Building on Basic Science
Catalytic antibodiesXwhich Lerner pioneered simultaneously with Scripps Research Professor Peter Schultz, Ph.D., (then at the University of California, Berkeley) in the 1980sXare large proteins naturally produced by the immune system and found in the bloodstream.
Unlike ordinary antibodies, which recognize a wide range of foreign pathogens (such as bacteria and viruses) then alert the immune system to the presence of the invaders, catalytic antibodies recognize the transition state for chemical reactions. Catalytic antibodies can also catalyze chemical reactions, similar to enzymes.
These special properties of catalytic antibodies open the door to some interesting chemistry.
Take Barbas, Lerner, and then-postdoctoral fellow Jurgen Wagner's paper published in the December 15, 1995 (Vol. 270) issue of the journal Science, which laid the foundation for the CovX technology years later.
In the study, the scientists used a technique called reactive immunization, which enabled antibodies to catalyze reactions previously thought impossible. Specifically, the technique allowed scientists to use antibodies to catalyze carbon-carbon bond formation and to bind catalytic antibodies to antigens covalently. (In general, antibodies bind non-covalently with their substrates.)
"The key feature of the reactive immunization approach is that it allowed us to define in rather precise chemical detail the amino acids within the active site of the antibody that would perform the chemical reaction," said Barbas, adding that the antibodies the team developed with reactive immunization remain the most highly active catalysts ever made.
|Contact: Keith McKeown|
Scripps Research Institute