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

Wadih Ghattas, Lur Cotchico-Alonso, Jean Didier Maréchal, Agathe Urvoas, Maëva Rousseau, Jean Pierre Mahy, Rémy Ricoux

Research output: Contribution to journalArticleResearchpeer-review

19 Citations (Scopus)

Abstract

© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. 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.
Original languageEnglish
Pages (from-to)433-440
JournalChemBioChem
Volume17
Issue number5
DOIs
Publication statusPublished - 2 Mar 2016

Keywords

  • artificial metalloenzymes
  • biocatalysis
  • copper complexes
  • diels-alder cyclization reaction
  • molecular modeling

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