Development of DNA Metalloenzymes Using a Rational Design Approach and Application in the Asymmetric Diels-Alder Reaction

We report here DNA metalloenzymes that catalyzed the asymmetric Diels-Alder reactions with high conversion, excellent endo/exo selectivities, and enantioselectivities up to -97% ee. Their catalytic-pocket architectures were organized using a rational design strategy based on the Cu(II) ion, the composition of nucleobases, and the incorporation of flexible linkers. Without using the mirror image of B-DNA, DNA metalloenzymes afforded the opposite enantiomer of the Diels-Alder product compared with those obtained using a supramolecular Cu(II)-dmbpy/st-DNA catalyst system. Furthermore, we devised DNA metalloenzymes without the incorporation of an artificial binding ligand and successfully performed Diels-Alder carbon-carbon bond-forming reactions. This study provides a new perspective on the catalytic repertoire of nucleic acids in the realm of protein-dominated metalloenzymes.