TY - JOUR
T1 - Artificial Metalloenzymes with the Neocarzinostatin Scaffold: Toward a Biocatalyst for the Diels-Alder Reaction
AU - Ghattas, Wadih
AU - Cotchico-Alonso, Lur
AU - Maréchal, Jean Didier
AU - Urvoas, Agathe
AU - Rousseau, Maëva
AU - Mahy, Jean Pierre
AU - Ricoux, Rémy
PY - 2016/3/2
Y1 - 2016/3/2
N2 - © 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.
AB - © 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.
KW - artificial metalloenzymes
KW - biocatalysis
KW - copper complexes
KW - diels-alder cyclization reaction
KW - molecular modeling
U2 - 10.1002/cbic.201500445
DO - 10.1002/cbic.201500445
M3 - Article
VL - 17
SP - 433
EP - 440
JO - ChemBioChem
JF - ChemBioChem
SN - 1439-4227
IS - 5
ER -