Hapten carbonyl

Figure 13 Structure of haptens 14 and 15 designed to elicit monoclonal antibodies that would be able to catalyze the reduction of carbonyl compounds by nicotinamide derivatives.

Metabolic activation of a,/ -unsaturated oximes, such as 46, leads to the conclusion that this class of unsaturated oximes are pro-haptens. They can undergo epoxidation that eventually produces reactive nitroso intermediates which act as strong contact sensitizers . Here, the oxime function plays a major role in the chemical activation that results in the reactive nitrosoaUcenes. It was further pointed by the authors that oximes can be hydrolyzed in vivo to the corresponding carbonyl compounds which are potential allergens. 

An alternate complementary approach toward catalytic antibody generation that could overcome the entropic disadvantage of preorganization of the amine cofactor with the Ab catalyst was investigated. A phosphinate (Scheme 5.64) was designed to mimic the expected transition state for the addition of a pheny-lacetone derived enolate to the carbonyl of benzaldehyde. An Ab raised against this hapten was expected to catalyze the aldol condensation of benzylacetone and benzaldehyde by both proximity and electrostatic effects. However, while... 

Synthetic procedures used to prepare antigenic hapten-carrier conjugates are reviewed by Erlanger. Procedures that have proven successful with hapten molecules that possess carboxyl, amino, hydroxyl, and carbonyl groups are fairly routine. The preparation of hapten-carrier conjugates by other synthetic routes is also considered. 

Enantioselective protonation of prochiral enols or enolates, which provides synthetic access to optically active carbonyl compounds, is an elegantly simple test reaction for enantioselective reagents and catalysts, for which a number of examples have been described [80]. The only reaction described with alkyl enol ethers concerns the highly enantioselective protonation of enol ethers such as 55 by catalytic antibody 14D9, an antibody raised against hapten 10 [81]. Antibody 14D9 has a practical turnover of /c-at = 0.4 for substrate 55 and produces... 

Most antibody-catalyzed reactions are hydrolytic processes, which are highly exergonic in aqueous environment. / -Elimination of /J-hydroxyketones to form a,/ -unsaturated ketones is a rare case of a dehydration reaction proceeding exothermically in aqueous environment. Catalytic antibodies promoting -elimination of /1-hydroxy and /1-halo-carbonyl compounds have been described [52]. The most interesting from a synthetic viewpoint concerns compound 30, which can be dehydrofluorinated to Z-olefin 32 using catalytic antibody 1D4 raised against hapten 29, while the uncatalyzed reaction exclusively yields the more stable E-olefin 31 (Scheme 11) [53]. Dehydratase activity also arises in aldolase antibodies and will be discussed below in that context. 

Fig. 2 (A) Antibody 43C9. elicited against a phosphonamidate hapten, catalyzes the hydrolysis of an activated amide. (B) Evidence reveals that antibody 43C9 employs a covalent catalytic mechanism. HisL91 is the nucleophile that attacks the substrate s amide carbonyl. Residue HisH35 assists in transition-state stabilization, while Trj L36 and TryH95 are probably involved in proton transfer.

Matsuda, T., Nakashima, I., Kato, Y. and Nakamura, R. Antibody response to haptenic sugar antigen immunodominancy of protein-bound lactose formed by amino-carbonyl reaction. Mol. Immunol 1987.24,421-425. 

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