Catalytic antibodies applications

Like many other antibodies, the activity of antibody 14D9 is sufficient for preparative application, yet it remains modest when compared to that of enzymes. The protein is relatively difficult to produce, although a recombinant format as a fusion vdth the NusA protein was found to provide the antibody in soluble form with good activity [20]. It should be mentioned that aldolase catalytic antibodies operating by an enamine mechanism, obtained by the principle of reactive immunization mentioned above [15], represent another example of enantioselective antibodies, which have proven to be preparatively useful in organic synthesis [21]. One such aldolase antibody, antibody 38C2, is commercially available and provides a useful alternative to natural aldolases to prepare a variety of enantiomerically pure aldol products, which are otherwise difficult to prepare, allovdng applications in natural product synthesis [22]. 

Catalytic alumina, 2 391 Catalytic antibodies, 3 671-672 Catalytic antibodies, 11 4 Catalytic applications... 

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]. 

Busch et al. studied the applicability of CZE to the examination of hapten-antibody complex formation (11). The catalytic antibodies examined have been used to accelerate a Diels-Alder reaction. Association constants of two hapten-antibody complexes were investigated and compared to the ELISA method. The samples contained buffer, hapten, and antibody. The constants obtained with CZE are a factor of 3-5 larger than those found with the ELISA method. The free-hapten concentration is measured directly this allows confirmation of the stoichiometric model. Because of the poor concentration sensitivity of UV detection, the application of an extended optical path length such as a bubble cell is necessary to obtain reliable binding parameters. 

N. K. Kochetkov, Catalytic antibodies Possible applications in organic synthesis, Russian Chem. Rev., 67 (1998) 999-1029. 

Hanson CV, Nishiyama Y et al (2005) Catalytic antibodies and their applications. Curr Opin Biotechnol 16 631-636... 

In this section is an overview of some historical aspects of enzyme studies with special emphasis on new methods of purification, structure determination, and research on the reaction mechanism of an enzyme. Enzyme application for medical and industrial use and development of novel enzymes such as catalytic RNA (ribozyme) and catalytic antibody (abzymes) are also briefly described. 

As the above examples attest, catalytic antibody technology can be a powerful and versatile approach for creating new catalysts. Not surprisingly, various practical applications have been envisaged to capitalize on this capability. 

Current and potential applications of catalytic antibodies in reactive immunization, therapy, biochemical analysis and biotechnology have been discussed (Schultz and Lemer, 1995 Rader and List, 2000 Blackburn and Garcon, 2000 Hilvert, 2000 Rader and List, 2000 Blackburn and Garcon, 2000 Vayron, 2000a,b). 

Since natural enzymes are unable to accept all of the unnatural substrates that they are called upon to accept for organic synthesis applications, alternative biocatalysts with expanded substrate specificity are needed. One approach toward the generation of new biocatalysts is to exploit the molecular diversity of the immune system by recruiting catalytic antibodies as protein catalysts. 

This mechanism-based approach for eliciting catalytic antibodies has demonstrated promising opportunities for biocatalyst generation, and for the first time, it shows the possibility of being competitive with natural enzymes. The application of this second-generation catalytic antibody in the synthesis of several natural products gives credence to their potential applicability and demonstrates their scope. 

In the case of biocatalysis, enzymes [3] and catalytic antibodies [4] have attracted most attention. Since enzymes are inherently the more active catalysts, they have been used most often. Indeed, many industrial processes for the enantioselective production of certain chiral intermediates are based on the application of enzymes, as in the lipase-catalyzed kinetic resolution of an epoxy-ester used in the production of the anti-hypertensive therapeutic Diltiazem [5]. Recently, it has been noted that there seems to be a trend in industry to use enzymes more often than in the past... 

Selection of a catalytic antibody via its binding to a TSA assumes that this binding will be predictive of the catalytic efficiency of the selected antibody. An intriguing application in which the selection of an antibody via a process based directly on catalytic efficiency was reported by Gao et al. (132). The acylated tripeptide amides 10.14a,b and esters 10.15a,b were used as substrates for hydrolysis to acids 10.16a,b (Fig. 10.21), and a catalytic antibody was looked for through the generation a display... 

A complete assessment of catalyst performance must in addition address product inhibition and catalyst inactivation. For preparative applications, the final criterion concerns the absolute value of kcao which expresses how much product can be obtained from the catalysts per unit of time. As will be seen below, several catalytic antibodies indeed turn out to perform excellently in all respects. 

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