Nucleic acids are the most vital biomolecules that store and transmit genetic information in biological systems. The structures and structural changes of nucleic acids are essential for the implementation and regulation of biological functions, making nucleic acids potential therapeutic targets. Therefore, the characterization and determination of nucleic acid structures would be indispensable for the mechanism study, clinical diagnosis, and drug design. Among these structures of interest, G-quadruplex is a common stable non-classical four-stranded motif that can be classified into three different types of topologies, i.e. parallel, antiparallel, and hybrid. Using synthetic supramolecular receptors and a set of carefully selected dye molecules, we have developed a fast, label-free Host-Guest sensing array to achieve the discrimination and classification of different DNA G-quadruplex topologies <i>via</i> fluorescence measurement that is easily accessible in normal lab settings. Moreover, DNA G-quadruplexes with the same topology but different sequences or different numbers of stacked G-tetrads can also be well differentiated by this sensing array. Currently, we are extending this Host-Guest sensing array to discriminate different DNA secondary structural motifs, such as hairpin, G4 with a bulge or vacancy, H-DNA, ssDNA, etc. We will further apply our Host-Guest array to sense the structural changes triggered by modifications and mutations in nucleic acid sequences.

Applying a host-guest sensing array for the classification of DNA structural motifs

ACS Fall 2021

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