Photoswitching of DNA Hybridization Using a Molecular Motor

[Image: see text] Reversible control over the functionality of biological systems via external triggers may be used in future medicine to reduce the need for invasive procedures. Additionally, externally regulated biomacromolecules are now considered as particularly attractive tools in nanoscience and the design of smart materials, due to their highly programmable nature and complex functionality. Incorporation of photoswitches into biomolecules, such as peptides, antibiotics, and nucleic acids, has generated exciting results in the past few years. Molecular motors offer the potential for new and more precise methods of photoregulation, due to their multistate switching cycle, unidirectionality of rotation, and helicity inversion during the rotational steps. Aided by computational studies, we designed and synthesized a photoswitchable DNA hairpin, in which a molecular motor serves as the bridgehead unit. After it was determined that motor function was not affected by the rigid arms of the linker, solid-phase synthesis was employed to incorporate the motor into an 8-base-pair self-complementary DNA strand. With the photoswitchable bridgehead in place, hairpin formation was unimpaired, while the motor part of this advanced biohybrid system retains excellent photochemical properties. Rotation of the motor generates large changes in structure, and as a consequence the duplex stability of the oligonucleotide could be regulated by UV light irradiation. Additionally, Molecular Dynamics computations were employed to rationalize the observed behavior of the motor–DNA hybrid. The results presented herein establish molecular motors as powerful multistate switches for application in biological environments.