Artificial Metalloenzymes with the Neocarzinostatin Scaffold: Toward a Biocatalyst for the Diels-Alder Reaction - Archive ouverte HAL
Article Dans Une Revue ChemBioChem Année : 2016

Artificial Metalloenzymes with the Neocarzinostatin Scaffold: Toward a Biocatalyst for the Diels-Alder Reaction

Wadih Ghattas
Lur Cotchico-Alonso
  • Fonction : Auteur
Jean-Didier Maréchal
  • Fonction : Auteur
Maëva Rousseau
  • Fonction : Auteur
Jean-Pierre Mahy
  • Fonction : Auteur
Rémy Ricoux

Résumé

A copper(II) cofactor coupled to a testosterone anchor, copper(II)-(5-(Piperazin-1-yl)-1,10-phenanthroline)testosterone-17-hemisuccinamide (10) was synthesized and associated with a neocarzinostatin variant, NCS-3.24 (KD =3 μm), thus generating a new artificial metalloenzyme by following a "Trojan horse" strategy. Interestingly, the artificial enzyme was able to efficiently catalyze the Diels-Alder cyclization reaction of cyclopentadiene (1) with 2-azachalcone (2). In comparison with what was observed with cofactor 10 alone, the artificial enzymes favored formation of the exo products (endo/exo ratios of 84:16 and 62:38, respectively, after 12 h). Molecular modeling studies assigned the synergy between the copper complex and the testosterone (KD =13 μm) moieties in the binding of 10 to good van der Waals complementarity. Moreover, by pushing the modeling exercise to its limits, we hypothesize on the molecular grounds that are responsible for the observed selectivity.

Dates et versions

hal-02393787 , version 1 (04-12-2019)

Identifiants

Citer

Wadih Ghattas, Lur Cotchico-Alonso, Jean-Didier Maréchal, Agathe Urvoas, Maëva Rousseau, et al.. Artificial Metalloenzymes with the Neocarzinostatin Scaffold: Toward a Biocatalyst for the Diels-Alder Reaction. ChemBioChem, 2016, 17 (5), pp.433--440. ⟨10.1002/cbic.201500445⟩. ⟨hal-02393787⟩
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