Catalytic antibodies ester hydrolysis

FIGURE 14.25 Catalytic antibodies are designed to specifically bind the transition-state intermediate in a chemical reaction, (a) The intramolecnlar hydrolysis of a hydroxy ester to yield as products a S-lactone and the alcohol phenol. Note the cyclic transition state, (b)... 

Catalysis, enzymatic, physical organic model systems and the problem of, 11,1 Catalysis, general base and nucleophilic, of ester hydrolysis and related reactions, 5,237 Catalysis, micellar, in organic reactions kinetic and mechanistic implications, 8,271 Catalysis, phase-transfer by quaternary ammonium salts, 15,267 Catalytic antibodies, 31,249... 

As we shall see later, most catalytic antibodies achieve rate accelerations in the range 103 to 106. It follows that for a very slow reaction, e.g. the alkaline hydrolysis of a phosphate diester with A 0h 10-u m 1 s 1 direct observation of the reaction is going to be experimentally problematic. Given that concentrations of catalytic antibodies employed are usually in the 1-10 /am range, it has proved far more realistic to target the hydrolysis of an aliphatic ester, with /c0h 0.1 m-1 s-1 under ambient conditions. 

Since then, catalytic antibodies which catalyze different chemical reactions have been described. The reactions range from ester or carbonate hydrolysis to carbon-carbon bond forming reactions, bimolecular amide formation or peptide bond cleavage, so the application of catalytic antibodies to general synthetic organic chemistry seems to be very promising [22]. 

Figure 2 Ester hydrolysis. Design of a stable analogue of the tetrahedral transition state to be used as a hapten to generate catalytic antibodies with an esterase activity.

Many of the 60 known reactions catalyzed by monoclonal antibodies involve kinetically favored reactions e.g., ester hydrolysis), but abzymes can also speed up kinetically disfavored reactions. Stewart and Benkovic apphed transition-state theory to analyze the scope and limitations of antibody catalysis quantitatively. They found the observed rate accelerations can be predicted from the ratio of equilibrium binding constants of the reaction substrate and the transition-state analogue used to raise the antibody. This approach permitted them to rationalize product selectivity displayed in antibody catalysis of disfavored reactions, to predict the degree of rate acceleration that catalytic antibodies may ultimately afford, and to highlight some differences between the way that they and enzymes catalyze reactions. 

Figure 18.2 Hydrolysis of carbonates and esters by catalytic antibodies (Lerner, 1991).

---