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

Jun Guo; Danyu Wang; Evangelia Pantatosaki; Huihui Kuang; George K Papadopoulos; Michael Tsapatsis; Efrosini Kokkoli

doi:10.1021/jacsau.1c00513

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

JACS Au. 2022 Jan 20;2(2):483-491. doi: 10.1021/jacsau.1c00513. eCollection 2022 Feb 28.

Authors

Jun Guo¹, Danyu Wang^{1

2}, Evangelia Pantatosaki³, Huihui Kuang¹, George K Papadopoulos^{3

4}, Michael Tsapatsis^{1

2

5}, Efrosini Kokkoli^{1

2}

Affiliations

¹ Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, Maryland 21218, United States.
² Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218, United States.
³ School of Chemical Engineering, National Technical University of Athens, 15780 Athens, Greece.
⁴ Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
⁵ Applied Physics Laboratory, Johns Hopkins University, Laurel, Maryland 20723, United States.

Abstract

A DNA-based artificial metalloenzyme (ArM) consisting of a 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 2 contiguous central pairs (G for guanine and C for cytosine) catalyzes the highly enantioselective Diels-Alder reaction, Michael addition, and Friedel-Crafts alkylation 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 inverts 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.