A Photoresponsive Intramolecular Triplex Motif That Enables Rapid and Reversible Control of Aptamer Binding Activity.
Tuan TrinhIan Andrew Paul ThompsonFinley ClarkJacob M RemingtonMichael EisensteinJianing LiHyongsok Tom SohPublished in: ACS nano (2022)
DNA switches that can change conformation in response to certain wavelengths of light could enable rapid and noninvasive control of chemical processes for a wide range of applications. However, most current photoresponsive DNA switches are limited by either irreversible switching or reversible switching with impractically slow kinetics. Here, we report the design of an intramolecular triplex photoswitch (TPS) design based on single-stranded DNA that undergoes rapid and reversible photoswitching between folded and unfolded states through isomerization of internal azobenzene modifications. After optimizing the performance of our photoswitch design, we used molecular dynamics simulations to reveal how individual azobenzenes contribute to the stabilization or destabilization of the triplex depending on their photoisomerization state. By coupling our TPS to an existing aptamer, we can reversibly modulate its binding affinity with less than 15 s of UV light exposure. We further demonstrate reproducible shifting in affinity over multiple cycles of UV and blue light irradiation without substantial photobleaching.
Keyphrases
- molecular dynamics simulations
- circulating tumor
- cell free
- single molecule
- loop mediated isothermal amplification
- gold nanoparticles
- nucleic acid
- binding protein
- sensitive detection
- molecular docking
- dna binding
- aqueous solution
- circulating tumor cells
- energy transfer
- radiation therapy
- single cell
- magnetic nanoparticles
- genome wide