Photoswitching of DNA Hybridization Using a Molecular Motor

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.