title: Hemoabzymes: towards new biocatalysts for selective oxidations.
abstract: Catalytic antibodies with a metalloporphyrin cofactor or <<hemoabzymes>>, used as models for hemoproteins like peroxidases and cytochrome P450, represent a promising 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 antibodies, raised against various free-base, N-substituted Sn-, Pd- or Fe-porphyrins. Five of them exhibited, in the presence of the corresponding Fe-porphyrin cofactor, a significant peroxidase activity, with k(cat)/K(m) values of 3.7 x 10(3) - 2.9 x 10(5) M(-1) min(-1). This value remained, however, low when compared to that of peroxidases. This strategy has also led to a few models of cytochrome P450. The best of them, raised against a water-soluble tin(IV) porphyrin containing an axial alpha-naphtoxy ligand, was reported to catalyze the stereoselective oxidation of aromatic sulfides by iodosyl benzene using a Ru(II)-porphyrin cofactor. The relatively low efficiency of the porphyrin-antibody complexes is probably due, at least in part, to the fact that no proximal ligand of Fe has been induced in those antibodies. We then proposed to use, as a hapten, microperoxidase 8 (MP8), a heme octapeptide in which the imidazole side chain of histidine 18 acts as a proximal ligand of the iron atom. This led to the production of seven antibodies recognizing MP8, the best of them, 3A3, binding it with an apparent binding constant of 10(-7) M. The corresponding 3A3-MP8 complex was found to have a good peroxidase activity characterized by a k(cat)/K(m) value of 2 x 10(6) M(-1) min(-1), which constitutes the best one ever reported for an antibody-porphyrin complex. Active site topology studies suggest that the binding of MP8 occurs through interactions of its carboxylate substituents with amino acids of the antibody and that the protein brings a partial steric hindrance of the distal face of the heme of MP8. Consequently, the use of the 3A3-MP8 complexes for the selective oxidation of substrates, such as sulfides, alkanes and alkenes will be undertaken in the future.
authors.affiliation: Laboratoire de Chimie Bioorganique et Bioinorganique, FRE 2127 CNRS, Institut de Chimie Moléculaire d'Orsay, Bâtiment 420, Université de Paris-sud XI, 91405 Cedex, Orsay, France
authors.forename: Rémy
authors.initials: R
authors.lastname: Ricoux
authors.forename: Hélène
authors.initials: H
authors.lastname: Sauriat-Dorizon
authors.forename: Elodie
authors.initials: E
authors.lastname: Girgenti
authors.forename: Dominique
authors.initials: D
authors.lastname: Blanchard
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Mahy
mesh_terms: D000818:Animals; D017151:Antibodies, Catalytic / Q000096:biosynthesis / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000378:metabolism*; D002384:Catalysis; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000276:immunology / Q000378:metabolism*
chemical_list: D017151:Antibodies, Catalytic; D000911:Antibodies, Monoclonal; D010544:Peroxidases; C021799:microperoxidase