Antibody catalysis

Understanding and Predicting Biological Catalysis Antibody Catalysis of Disfavored Cyclization Reactions... 

Comparison of 34E4 with a less proficient catalyst shows that merely positioning a carboxylate in a hydrophobic binding pocket does not result in efficient general base catalysis. Antibody 4B2, generated against cationic amidinium salt 14 (Scheme 4.5),... 

A particularly efficient mechanism for manipulating the entropic issue to attain rate acceleration is through covalent catalysis. Antibody 21H3 is a remarkably efficient catalyst for the transesterification reaction between sec-phenethyl alcohol and an enolic ester in water to form the corresponding chiral ester (Fig. 

Pollack, 5.J., Jacobs, J.W., Schultz, RG. Selective chemical catalysis by an antibody. Science 234 1570-1573,... 

Janda, K. D., 1997. Chemical selection for catalysis in combinatorial antibody libraries. Science 275 945. 

Hilvert D. Antibody Catalysis of Carbon-Carbon Bond Formation and Cleavage... 

Keywords catalytic antibodies, Diels-Alder reactions and catalysis... 

The molecular mechanism of the enantioselective protonation reaction by antibody 14D9 was revealed by a crystal structure analysis [19[. A catalytic carboxyl group AspH 101 was found at the bottom of the catalytic pocket and found to be necessary for catalysis by mutagenesis to Asn or Ala. The mechanism or protonation involves an overall syn addition of water to the enol ether in a chiral binding pocket ensuring complete enantioselectivity (Figure 3.4). 

Conventional ion-selective electrodes have been used as detectors for immunoassays. Antibody binding measurements can be made with hapten-selective electrodes such as the trimethylphenylammonium ion electrode Enzyme immunoassays in which the enzyme label catalyzes the production of a product that is detected by an ion-selective or gas-sensing electrode take advantage of the amplification effect of enzyme catalysis in order to reach lower detection limits. Systems for hepatitis B surface antigen and estradiol use horseradish peroxidase as the enzyme label and... 

Homogeneous immunoassays rely on a change in the intensity of the label signal that occurs when labeled antigen binds with antibody. When the label is an antibody, a reduction in the rate of enzyme catalysis forms the basis for the assay. This technique... 

One of the best ways to ensure retention of activity in protein molecules is to avoid doing chemistry at the active center. The active center is that portion of the protein where ligand, antigen, or substrate binding occurs. In simpler terms, the active center (or active site) is that part that has specific interaction with another substance (Means and Feeney, 1971). For the preparation of enzyme derivatives, it is important to protect the site of catalysis where conversion of substrate to product happens. For instance, when working with antibody molecules, it is crucial to stay away from the two antigen binding sites. 

Antibody reduction usually is done in the presence of EDTA to prevent re-oxidation of the sulfhydryls by metal catalysis. In phosphate buffer at pH 6-7 and 4°C, one report stated that the number of available thiols decreased only by about 7 percent in the presence of EDTA over a 40-hour time span. In the absence of EDTA, this sulfhydryl loss increased to 63-90 percent... 

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... 

The library of natural catalysts has very little to offer for the catalysis of Diels-Alder (and the reverse) reactions (Diels-Alderases)[139]. For this reason one of the intriguing areas of biomimickry, namely the formation and use of antibodies exhibiting catalytic activity, has focused on [4 + 2] reactions to try to furnish proteins possessing useful catalytic properties. Thus in early studies a polyclonal catalytic antibody raised to hapten (57)[140] showed a modest rate enhancement for the reaction depicted in Scheme 48. 

In Figure 3 a schematic view is presented of how primary catalysis is achieved. Besides this necessary and sufficient condition required to set up catalysis, there may be some other factors producing an enhancement of the catalytic event. General acid and general base catalytic groups, metal coordination sphere appropriately prepared are examples of catalytic subsidiary effects. The pure molding factor is usually achieved by catalytic antibodies techniques. 

Gouvemeur, V. E., Houk, K. N., Pascual-Teresa, B., Beno, B., Janda, K. D. and Lemer, R. A. Control ofthe exo and endo pathways ofthe Diels-Alder reaction by antibody catalysis, Science, 262 (1993), 204-208... 

Shabat, D., Itzhaky, H., Reymond, J.-L. and Keinan, E. Antibody catalysis of a reaction otherwise strongly disfavoured in water, Nature, 374 (1995), 143-146... 

To date, most theozymes have been used to quantitate the effects of noncovalent interactions on catalysis by enzymes and catalytic antibodies (abzy-mes).131 Theozymes have provided insight into the... 

Gruber, K Zhou, B. Houk, K N. Lemer, R. A. Shevlin, C. G. Wilson, I. A. Structural Basis for Antibody Catalysis of a Disfavored Ring Closure Reaction Biochemistry 1999, 38, 7062-7074. 

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