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Dissection Of An Antibody-Catalyzed Reaction, Jon D. Stewart, Joseph F. Krebs, Gary Siuzdak, Anthony J. Berdis, David B. Smithrud, Stephen J. Benkovic

Chemistry Faculty Publications

Antibody 43C9 accelerates the hydrolysis of a p-nitroanilide by a factor of 2.5 x 10(5) over the background rate in addition to catalyzing the hydrolysis of a series of aromatic esters. Since this represents one of the largest rate accelerations achieved with an antibody, we have undertaken a series of studies aimed at uncovering the catalytic mechanism of 43C9. The immunogen, a phosphonamidate, was designed to mimic the geometric and electronic characteristics of the tetrahedral intermediate that forms upon nucleophilic attack by hydroxide on the amide substrate. Further studies, however, revealed that the catalytic mechanism is more complex and involves …