Asymmetric G-Quadruplex DNA Scaffolds and their Application as Combinatorial Sensors and Molecular Security Systems

Conventional methods for creating synthetic receptors are generally limited by the need to use water-soluble building blocks and performing multistep organic synthesis, which complicate using such receptors as biomimetics and sensors. To address this problem, we have developed a simple, versatile and robust method for preparing sets of water-soluble synthetic receptors through the self-assembly of oligonucleotides (ODNs) into asymmetric DNA G-quadruplex structures. By modifying these ODNs with supramolecular recognition elements and distinct fluorescent reporters (Figure 1) we have demonstrated the possibility of creating a novel type of pattern-generating fluorescent probes that can discriminate among multiple different analytes, such as drugs of abuse, in a high-throughput manner. We have also shown that these sensors can function as molecular-scale security systems that can authorize four different users simultaneously.

Figure 1. Four DNA strands appended with different linkers and fluorophores can self-assemble into a unique asymmetric quadruplex structure. The resulting analytical device can generate a wide range of distinct emission fingerprints upon binding to different analytes.