New activities of a catalytic antibody with a peroxidase activity: formation of Fe(II)-RNO complexes and stereoselective oxidation of sulfides.
In order to estimate the size of the cavity remaining around the heme of the 3A3-microperoxidase 8 (MP8) hemoabzyme, the formation of 3A3-MP8-Fe(II)-nitrosoalkane complexes upon oxidation of N-monosubstituted hydroxylamines was examined. This constituted a new reaction for hemoabzymes and is the first example of fully characterized Fe(II)-metabolite complexes of antibody-porphyrin. Also, via a comparison of the reactions with N-substituted hydroxylamines of various size and hydrophobicity, antibody 3A3 was confirmed to bring about a partial steric hindrance on the distal face of MP8. Subsequently, the influence of the antibody on the stereoselectivity of the S-oxidation of sulfides was examined. Our results showed that MP8 alone and the antibody-MP8 complex catalyze the oxidation of thioanisole by H(2)O(2) and tert-butyl hydroperoxide, following a peroxidase-like two-step oxygen-transfer mechanism involving a radical-cation intermediate. The best system, associating H(2)O(2) as oxidant and 3A3-MP8 as a catalyst, in the presence of 5% tert-butyl alcohol, led to the stereoselective S-oxidation of thioanisole with a 45% enantiomeric excess in favour of the R isomer. This constitutes the highest enantiomeric excess reported to date for the oxidation of sulfides catalyzed by hemoabzymes.
Ricoux
Rémy
R
Laboratoire de Chimie Bioorganique et Bioinorganique, Institut de Chimie Moléculaire et des Matériaux d'Orsay, Université Paris-Sud XI, Orsay, France.
Lukowska
Edyta
E
Pezzotti
Fabio
F
Mahy
Jean-Pierre
JP
D000818:Animals; D001665:Binding Sites; D045304:Cytochromes c / Q000737:chemistry; D006418:Heme / Q000737:chemistry*; D006736:Horses; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000494:pharmacology; D006898:Hydroxylamines / Q000737:chemistry; D007501:Iron / Q000737:chemistry*; D007700:Kinetics; D008954:Models, Biological; D008956:Models, Chemical; D010100:Oxygen / Q000378:metabolism*; D010544:Peroxidases / Q000737:chemistry*; D011166:Porphyrins / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013237:Stereoisomerism; D013440:Sulfides / Q000737:chemistry; D013997:Time Factors; D014466:Ultraviolet Rays; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D006898:Hydroxylamines; D011166:Porphyrins; D013440:Sulfides; D006418:Heme; D045304:Cytochromes c; D020122:tert-Butylhydroperoxide; C093850:methylphenylsulfide; D006861:Hydrogen Peroxide; D007501:Iron; D010544:Peroxidases; C021799:microperoxidase; D010100:Oxygen