Antibodies proximity effects

Pericyclic processes comprise a broad and important class of concerted reactions of both theoretical and practical interest. These transformations, which are especially useful in the construction of carbon-carbon bonds,93 include electrocyclic reactions, sigmatropic rearrangements, and cycloadditions. Because they are not typically subject to general acid-general base chemistry but can be highly sensitive to strain and proximity effects, they are attractive targets for antibody catalysis. 

Other approaches have been developed to generate catalytic antibodies including covalent catalysis, proximity effects, and general acid-base catalysis [7]. In addition, strategies have been developed to directly select immu-... 

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... 

Further, for antibody catalysis the methyl ester is too small to be an effective epitope but the participation could be induced if an antibody were able to recruit cocaine from the chair conformation to the less stable boat form (see Fig. 4 for the structure) and reorient the syn-protonated amine and benzoyl ester into proximity. Antibodies can provide significant binding energy and in principle antibody binding could effect conformer selection and promotion of substrate-assisted catalysis. To examine this idea, a detailed computational analysis [89] of the energetics of this reaction was also performed for design of novel TSA structures for the alkaline hydrolysis of boat cocaine in comparison with the hydrolysis of chair cocaine. 

The potential contribution of cytokines to the chronic inflammatory process of asthma has been made possible mainly by looking for the presence of cytokines using immunohistochemical techniques on airway mucosal tissues obtained from the proximal airways of patients with asthma. In addition, localization of cytokine mRNA by in situ hybridization or its detection by polymerase chain reaction (PCR) has also been used, although expression of mRNA may not necessarily mean that the protein is produced. The exact contribution of individual cytokines can best be surmised from studies of their effect in cells in vitro or in animals, particularly with the use of blocking antibodies, although extrapolation to the situation in disease must be made with some caution. 

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