A Localized Enantioselective Catalytic Site on Short DNA Sequences and their Amphiphiles

Abstract

A DNA-based artificial metalloenzyme (ArM) consisting of copper (II) complex of 4,4'-dimethyl-2,2'-bipyridine (dmbipy-Cu) bound to double-stranded DNA (dsDNA) as short as 8 base pairs with only two contiguous central G•C pairs (G for guanine and C for cytosine), catalyzes highly enantioselective Diels-Alder reaction in water. Molecular simulations indicate that these minimal sequences provide a single site where dmbipy-Cu is groove-bound and able to function as an enantioselective catalyst. Enantioselective preference inverses when D-DNA is replaced with L-DNA. When the DNA is conjugated to a hydrophobic tail, the obtained ArMs exhibit enantioselective performance in a methanol-water mixture superior to that of non-amphiphilic dsDNA, and dsDNA-amphiphiles with more complex G•C-rich sequences.