The Study On Abzymes For Catalysed Selective Hydrolysis Of A-arylpropionic Acids Ester

Abzyme, or catalytic antibodies, is immunoglobulin that provided with catalytic activities. It is a newly developed research area derived from chemistry and biology. Because of highly selectivity and efficient catalysis, to date, catalytic antibodies have been shown to catalyze a vast array of different chemical processes, incorporating specificity, stereo- selectivity, and even the ability to route a reaction through a disfavored chemical pathway. In fact, antibodies have now been uncovered for reactions for which there are no known natural or man-made enzymes. It is great value both in theoretical and practical science. In this thesis, the selective hydrolysis of ibuprofen methyl ester by catalytic antibodies was investigated in detail.Theα-arylpropionic acid derivatives, also called "profens", including ibuprofen, naproxen, flurbiprofen, and etodolac, are an important group of nonsteroidal antiinflammatory drugs (NSAIDs). Most of these drugs are commonly administered as racemates, however the individual enantiomers differ in their pharmacological activity, mechanism of action and toxicity. This drug class is widely focused because of its various biologic properties that affect their clinical use. Ibuprofen is used in therapeutics as racemic mixtures for its antiinflammatory, analgesic, and antipyretic properties and the treatment of rheumatoid arthritis (RA) and osteoarthritis and so on. The configuration as well as the conformation of this enantiomer, S-ibuprofen, is regarded as the eutomer (the biological active enantiomer) of the ibuprofens. A resolution of ibuprofen has been achieved by enzyme-catalyzed or microbe cells enantioselective hydrolysis of the corresponding racemic esters,. But the report about selective hydrolysis of ibuprofen ester by catalytic antibodies is less.In this paper, we describe a new biocatalyst, catalytic antibodies, that produced ibuprofen from their corresponding racemic ester in enantiomerically pure (S)-configuration. The biocatalyzed hydrolysis reaction can be carried out with antibodies to achieve high enantioselectivity. To elicit catalytic antibodies for the ibuprofen methyl ester hydrolysis, the tetrahedron structure compound contained sulphur was designed and synthsis as hapten which is mimic of TSA, based on the transition state theory. The hapten was covalently attached to bovine serum albumin (BSA) to be used as immunogens. A catalytic antibodies were prepared from mice and sequential purification by ammonium sulfate precipitation and affinity chromatography. The catalytic activity of the catalytic antibody in the water-miscible organic-solvent system composed of a buffer solution and N, N-dimethylformamide (DMF) was studied. The asymmetric A3 hydrolysis of racemic ibuprofen ester, with 6% DMF in the buffer solution, a good conversion (48.7%) and high enantiomeric excess (>99%) could be reached.