Hemoabzymes different strategies for obtaining artificial hemoproteins based on antibodies |
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Authors: | Jean-Pierre Mahy Bernard Desfosses Solange de Lauzon Rebeca Quilez Bernadette Desfosses Laurence Lion Daniel Mansuy |
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Institution: | (1) Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, URA 400 CNRS, Université René Descartes, 45 Rue des Saints-Pères, 75270 Paris Cedex 06, France |
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Abstract: | Besides existing models of chemical or biotechnological origin for hemoproteins like peroxidases and cytochromes P450, catalytic
antibod ies (Abs) with a metalloporphyrin cofactor represent a promising alter native route to catalysts tailored for selective
oxidation reactions. A brief overview of the literature shows that, until now, the first strategy for obtaining such artificial
hemoproteins has been to produce antipor phyrin Abs, raised against various free-base, N-substituted, Sn-,Pd-,or Fe-porphyrins.
Four of them exhibited, in the presence of the corre sponding Fe-porphyrin cofactor, a significant peroxidase activity, with
kcat/Km values of 102 to 5 × 103/M/s. This value remained low when com pared to that of peroxidases, probably because neither a proximal ligand of the Fe,
nor amino acid residues participating in the catalysis of the heterolytic cleavage of the O—O bond of H2O2, have been induced in those Abs. This strategy has been shown to be insufficient for the elabo ration of effective models
of cytochromes P450, because only one set of Abs, raised againstmeso-tetrakis(para-carboxyvinylphenyl)porphyrin, was reported to catalyze the nonstereoselective oxidation of styrene by iodosyl benzene using
a Mn-porphyrin cofactor, and attempts to gener ate Abs having binding sites for both the substrate and the metallopor phyrin
cofactor, using as a hapten a porphyrin covalently linked to the substrate, were not successful. A second strategy is then
proposed, which involves the chemical labeling of antisubstrate Abs with a metallopor phyrin. As an example, preliminary results
are presented on the covalent linkage of an Fe-porphyrin to an antiestradiol Ab, in order to obtain semisynthetic catalytic
Abs able to catalyze the selective oxidation of steroids. |
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Keywords: | Hemoabzymes catalytic antibodies peroxidase cytochromes P450 metalloporphyrins oxidation steroids |
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