화학공학소재연구정보센터
Journal of the American Chemical Society, Vol.143, No.9, 3555-3561, 2021
Modular Design of G-Quadruplex MetalloDNAzymes for Catalytic C-C Bond Formations with Switchable Enantioselectivity
Metal-binding DNA structures with catalytic function are receiving increasing interest. Although a number of metalloDNAzymes have been reported to be highly efficient, the exact coordination/position of their catalytic metal center is often unknown. Here, we present a new approach to rationally develop metalloDNAzymes for Lewis acid-catalyzed reactions such as enantioselective Michael additions. Our strategy relies on the predictable folding patterns of unimolecular DNA G-quadruplexes, combined with the concept of metal-mediated base-pairing. Transition-metal coordination environments were created in G-quadruplex loop regions, accessible by substrates. Therefore, protein-inspired imidazole ligandoside L was covalently incorporated into a series of G-rich DNA strands by solid-phase synthesis. Iterative rounds of DNA sequence design and catalytic assays allowed us to select tailored metalloDNAzymes giving high conversions and excellent enantioselectivities (>= 99%). Based on their primary sequence, folding pattern, and metal coordination mode, valuable information on structure-activity relationships could be extracted. Variation of the number and position of ligand L within the sequence allowed us to control the formation of (S) and (R) enantiomeric reaction products, respectively.