Hemoabzymes. Different strategies for obtaining artificial hemoproteins based on antibodies.
Besides existing models of chemical or biotechnological origin for hemoproteins like peroxidases and cytochromes P450, catalytic antibodies (Abs) with a metalloporphyrin cofactor represent a promising alternative 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 antiporphyrin Abs, raised against various free-base, N-substituted, Sn-, Pd-, or Fe-porphyrins. Four of them exhibited, in the presence of the corresponding Fe-porphyrin cofactor, a significant peroxidase activity, with kcat/K(m) values of 10(2) to 5 x 10(3)/M/s. This value remained low when compared 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 elaboration of effective models of cytochromes P450, because only one set of Abs, raised against meso-tetrakis(para-carboxyvinylphenyl)porphyrin, was reported to catalyze the nonstereoselective oxidation of styrene by iodosyl benzene using a Mn-porphyrin cofactor, and attempts to generate Abs having binding sites for both the substrate and the metalloporphyrin 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 metalloporphyrin. 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.
Mahy
J P
JP
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, URA 400 CNRS, Université René Descartes, Paris, France. mahy@bisance.citi2.fr
Desfosses
B
B
de Lauzon
S
S
Quilez
R
R
Desfosses
B
B
Lion
L
L
Mansuy
D
D
D000818:Animals; D017151:Antibodies, Catalytic / Q000097:blood*; D001798:Blood Proteins / Q000276:immunology*; D003577:Cytochrome P-450 Enzyme System / Q000276:immunology / Q000378:metabolism; D006241:Haptens / Q000276:immunology; D006801:Humans; D008956:Models, Chemical; D011166:Porphyrins / Q000276:immunology
D017151:Antibodies, Catalytic; D001798:Blood Proteins; D006241:Haptens; D011166:Porphyrins; D003577:Cytochrome P-450 Enzyme System