Title
I-Motif/miniduplex hybrid structures bind benzothiazole dyes with unprecedented efficiencies: a generic light-up system for label-free DNA nanoassemblies and bioimaging
Author
Lili Shi, Pai Peng, Jiao Zheng, Qiwei Wang, Zhijin Tian, Huihui Wang, Tao Li
Year
2020
Journal
Nucleic Acids Research
Abstract
I-motif DNAs have been widely employed as robust modulating components to construct reconfigurable DNA nanodevices that function well in acidic cellular environments. However, they generally display poor interactivity with fluorescent ligands under these complex conditions, illustrating a major difficulty in utilizing i-motifs as the light-up system for label-free DNA nanoassemblies and bioimaging. Towards addressing this challenge, here we devise new types of i-motif/miniduplex hybrid structures that display an unprecedentedly high interactivity with commonly-used benzothiazole dyes (e.g. thioflavin T). A well-chosen tetranucleotide, whose optimal sequence depends on the used ligand, is appended to the 5′-terminals of diverse i-motifs and forms a minimal parallel duplex thereby creating a preferential site for binding ligands, verified by molecular dynamics simulation. In this way, the fluorescence of ligands can be dramatically enhanced by the i-motif/miniduplex hybrids under complex physiological conditions. This provides a generic light-up system with a high signal-to-background ratio for programmable DNA nanoassemblies, illustrated through utilizing it for a pH-driven framework nucleic acid nanodevice manipulated in acidic cellular membrane microenvironments. It enables label-free fluorescence bioimaging in response to extracellular pH change.
Instrument
J-1500
Keywords
Circular dichroism, DNA structure, Thermal stability, Chemical stability, Biochemistry