Supramolecular DNA-based catalysis in organic solvents

The distinct folding accompanied by its polymorphic character renders DNA G-quadruplexes promising biomolecular building blocks to construct novel DNA-based and supramolecular assemblies. However, the highly polar nature of DNA limits the use of G-quadruplexes to water as a solvent. In addition, the archetypical G-quadruplex fold needs to be stabilized by metal-cations, which is usually a potassium ion. Here, we show that a noncovalent PEGylation process enabled by electrostatic interactions allows the first metal-free G-quadruplexes in organic solvents. Strikingly, incorporation of an iron-containing porphyrin renders the self-assembled metal-free G-quadruplex catalytically active in organic solvents. Hence, these “supraG4zymes” enable DNA-based catalysis in organic media. The results will allow the broad utilization of DNA G-quadruplexes in nonaqueous environments. [Display omitted] •High-density noncovalent PEGylation drives DNA solubility in polar organic solvents•G-rich DNA can form G-quadruplexes in a metal-free organic phase•Solvent-selective and structure-specific catalysis in organic solvents are demonstrated Chemistry; Catalysis; Biomolecular engineering