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.

Harnessing DNA as a Designable Scaffold for Asymmetric Catalysis: Recent Advances and Future Perspectives

“…It was reported that the modular DNA hybrid catalysts with appended PEG molecules or amphipathic lipids could work well under various organic solvent or water-organic co-solvent conditions. [111][112][113] By the generation of more robust DNA in the presence of beneficent organic solvents or the establishment of micellar catalysis, an even broader range of applications is feasible.…”

“…Although these water‐compatible biohybrid catalysts display remarkable activity under aqueous conditions, their application has been limited because most organic compounds are barely soluble in water, hesitating the use of DNA‐based hybrid catalysts. It was reported that the modular DNA hybrid catalysts with appended PEG molecules or amphipathic lipids could work well under various organic solvent or water‐organic co‐solvent conditions [111–113] . By the generation of more robust DNA in the presence of beneficent organic solvents or the establishment of micellar catalysis, an even broader range of applications is feasible.…”