An Efficient Cyclic Di-AMP Based Artificial Metalloribozyme for Enantioselective Diels-Alder Reactions

The diverse structures of nucleic acids as scaffolds have brought the significant advancement for DNA-based enantioselective catalysis, yet RNA-based enantioselective catalysis is lacking investigation. Herein, we report a small, natural RNA of cyclic di-AMP (c-di-AMP) and Cu2+ ions assemble into an artificial metalloribozyme (c-di-AMP center dot Cu2+), that could effectively catalyze the enantioselective Diels-Alder reactions with up to 80 % ee. The enantioselective catalytic performance of c-di-AMP center dot Cu2+ has been studied by thorough investigations of different metal cofactors, c-di-AMP/Cu2+ molar ratios, additives, buffers and c-di-AMP analogues. In addition, the assembly of c-di-AMP center dot Cu2+ gives rise to 300-fold and 5-fold rate acceleration compared to the uncatalyzed reaction and Cu2+ ions, respectively. This work provides a simple and efficient strategy to construct the RNA-based catalysts that would expand the current nucleic acids-based catalysis and might hint the possible catalytic RNA in primordial chemistry.