Conformation-sensitive nucleoside analogues as topology-specific fluorescence turn-on probes for DNA and RNA G-quadruplexes

摘要: Development of probes that can discriminate G-quadruplex (GQ) structures and indentify efficient GQ binders on the basis topology nucleic acid type is highly desired to advance GQ-directed therapeutic strategies. In this context, we describe development minimally perturbing environment-sensitive pyrimidine nucleoside analogues, based a 5-(benzofuran-2-yl)uracil core, as topology-specific fluorescence turn-on for human telomeric DNA RNA GQs. The residues one loop regions (TTA) oligonucleotide (ON) sequences were replaced with 5-benzofuran-modified 2'-deoxyuridine uridine analogues. Depending position modification fluorescent analogues distinguish antiparallel, mixed parallel-antiparallel parallel stranded topologies from corresponding duplexes significant enhancement in intensity quantum yield. Further, these sensors enabled simple binding assay quantify topology- acid-specific small molecule ligands structures. Together, our results demonstrate are useful probes, which anticipated provide new opportunities study discover potential.