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

作者：Ghattas Wadih; Cotchico Alonso Lur; Marechal Jean Didier; Urvoas Agathe; Rousseau Maeva; Mahy Jean Pierre^*; Ricoux Remy^*

来源：ChemBioChem, 2016, 17(5): 433-440.

DOI：10.1002/cbic.201500445

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

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 (K-D=3m), 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 12h). Molecular modeling studies assigned the synergy between the copper complex and the testosterone (K-D=13m) 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.

• 出版日期2016-3
• 单位中国地震局