Functionalization of acyclic xenonucleic acid with modified nucleobases

Xenonucleic acids (XNAs), which are composed of artificial scaffolds and natural nucleobases, have unique hybridization properties that depend on the scaffold structure. Here, we functionalized the acyclic XNA serinol nucleic acid (SNA) with nonnatural nucleobases. A linear SNA probe functionalized with 5-perylenylethynyl uracil residues showed weak greenish-yellow excimer emission in the absence of target RNA and bright cyan-green monomer emission in the presence of target RNA. Probe hybridization was rapid and enabled the quantitative measurement of RNA with discrimination of single-base mismatches. We also designed a photoresponsive SNA with two 8-pyrenylvinyl adenine ((PV)A) residues. Irradiation with blue (455 nm) light caused [2 + 2] photocycloaddition between intrastrand As-PV, resulting in the dissociation of the SNA/RNA duplex, whereas irradiation with ultraviolet (340 nm) light induced cycloreversion of the (PV)A photodimer and SNA/RNA duplex reformation. Using a combination of 8-naphthylvinyl adenine ((NV)A) and (PV)A and irradiation with 465 nm, 405 nm, 340 nm, and 300 nm light, orthogonal control of the formation of SNA((NV)A-(NV)A)/RNA and SNA((PV)A-(NV)A)/RNA duplexes was demonstrated. Thus, nucleobase modifications further expand the utility of acyclic XNA in bionanotechnology.