Antibodies are structural and functional relatives of enzymes. Catalytic antibodies have been shown to catalyze a great number of chemical processes, with specifity, stereoselectivity and the ability to direct reaction through a disfavored chemical pathways. Of primary importance in successful catalytic antibody production is the rational design of the hapten that will be used for immunization. One of the most applied strategies employs antigens designed as stable analogs of transition-state of the target reactions [1]. In general, three different chemical groups are used to mimic tetrahedral reactions intermediates: amine or amide group, phosphonate group and sulfonyl group. Several classes of chemical reactions are, so far, catalyzed by abzymes formed against stable Transition State Analogs, like reduction reactions, hydrolysis reactions, cationic cyclizations, Diels-Alder reactions.

As a continuation of our previous studies [2,3], concerning the enantioselective reduction of pentoxifylline to 1-(5-R-hydroxyhexyl)-3,7-dimethylxanthine (lisofylline), we proposed method based on catalytic antibodies. For that purpose the two haptens were designed to generate monoclonal antibodies with following important features of binding pockets: a hydrophobic binding pocket for the xanthine ring and an acidic residue complementary to the oxyanionic transition state. Also, the haptens possesses a hydrocarbon linkers with carboxylic residues for a carrier protein coupling to provide sufficient immunogenicity of the antigens to elicit an immune response.

The N-oxide hapten has been synthesized from theobromine in four-step method. This hapten will be used for immunisation of mice as a keyhole limpet hemocyanin (KLH) conjugate for monoclonal antibodies production and for enzyme linked immunosorbent assay (ELISA) screening as a bovine serum albumin (BSA) conjugate.

Acknowledgements:

Financial support from the Jagiellonian University Medical College CR-122/2005 grant is gratefully acknowledged.

[1] Xu Y., Yamamoto N., Janda K.D. Bioorg. Med. Chem. 2004, 12, 5247-5368

[2] Kieć-Kononowicz K., Pękala E. (CMUJ). 2004, patent application P-369904

[3] Pękala E., Wójcik T.Sci. Pharm. 2005, 73(2), Supp.1, S67

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