title: Neocarzinostatin-based hybrid biocatalysts for oxidation reactions.
abstract: An anionic iron(III)-porphyrin-testosterone conjugate 1-Fe has been synthesized and fully characterized. It has been further associated with a neocarzinostatin variant, NCS-3.24, to generate a new artificial metalloenzyme following the so-called 'Trojan Horse' strategy. This new 1-Fe-NCS-3.24 biocatalyst showed an interesting catalytic activity as it was found able to catalyze the chemoselective and slightly enantioselective (ee = 13%) sulfoxidation of thioanisole by H2O2. Molecular modelling studies show that a synergy between the binding of the steroid moiety and that of the porphyrin macrocycle into the protein binding site can explain the experimental results, indicating a better affinity of 1-Fe for the NCS-3.24 variant than testosterone and testosterone-hemisuccinate themselves. They also show that the Fe-porphyrin complex is sandwiched between the two subdomains of the protein providing with good complementarities. However, the artificial cofactor entirely fills the cavity and its metal ion remains widely exposed to the solvent which explains the moderate enantioselectivity observed. Some possible improvements in the "Trojan Horse" strategy for obtaining better catalysts of selective oxidations are presented.
authors.affiliation: Institut de Chimie Moléculaire et des Matériaux d'Orsay, UMR 8182 CNRS, Laboratoire de Chimie Bioorganique et Bioinorganique, Bât. 420, Université Paris-sud, 91405 Orsay Cedex, France. Jean-Pierre.mahy@u-psud.fr.
authors.forename: Elodie
authors.initials: E
authors.lastname: Sansiaume-Dagousset
authors.forename: Agathe
authors.initials: A
authors.lastname: Urvoas
authors.forename: Kaouthar
authors.initials: K
authors.lastname: Chelly
authors.forename: Wadih
authors.initials: W
authors.lastname: Ghattas
authors.forename: Jean-Didier
authors.initials: JD
authors.lastname: Maréchal
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Mahy
authors.forename: Rémy
authors.initials: R
authors.lastname: Ricoux
mesh_terms: D055162:Biocatalysis; D006861:Hydrogen Peroxide / Q000737:chemistry; D008665:Metalloporphyrins / Q000138:chemical synthesis* / Q000737:chemistry; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013440:Sulfides / Q000737:chemistry; D009353:Zinostatin / Q000737:chemistry*
chemical_list: D008665:Metalloporphyrins; D013440:Sulfides; C000597208:iron(III)-5,10,15-tris(4-sulfonatophenyl)-20-(17'-succininimidyl-testosterone)porphyrin; D009353:Zinostatin; C093850:methylphenylsulfide; D006861:Hydrogen Peroxide