Switching on Supramolecular DNA Junction Binding Using a Human Enzyme
Year: 2025
Type: article
Abstract: Non‐canonical DNA junction structures are important in human disease and in nucleic acid nanoscience and there is a growing interest in how to bind and modulate them. A key next step is to exert “on command” control over such binding. Herein we develop a new metallo‐supramolecular triple‐helicate cylinder agent that is inert to DNA junction binding until activated by human enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) and its cofactor nicotinamide adenine dinucleotide phosphate (NADPH). This inactive cylinder bears six flexible arms each with a quinone group at the termini. Reduction by the enzyme leads to all six arms being removed, transforming the inert cylinder into a new and active metallo‐supramolecular agent that binds junctions. This gives the ability to “switch‐on” DNA junction formation and binding in response to the presence of two external stimuli – a human enzyme overexpressed in many disease states, and NADPH – and absence of inhibitor, giving NAND logic control. Modelling indicates the binding activation originates not in steric unblocking but changes in conformational flexibility. The work provides the foundation for and a route map toward future designs of sophisticated, inert, and supramolecular structures which are transformed by enzymes into new, active, and supramolecular structures for a variety of potential applications.
Source: Angewandte Chemie
Institution: University of Birmingham
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,790
OpenAlex ID: W4408479371