Nucleobase
mimicking small molecules able to reconfigure DNA are
a recently discovered strategy that promises to extend the structural
and functional diversity of nucleic acids. However, only simple, unfunctionalized
molecules such as cyanuric acid and melamine have so far been used
in this approach. In this work, we show that the addition of substituted
cyanuric acid molecules can successfully program polyadenine strands
to assemble into supramolecular fibers. Unlike conventional DNA nanostructure
functionalization, which typically end-labels DNA strands, our approach
incorporates functional groups into DNA with high density using small
molecules and results in new DNA triple helices coated with alkylamine
or alcohol units that grow into micrometer-long fibers. We find that
small changes in the small molecule functional group can result in
large structural and energetic variation in the overall assembly.
A combination of circular dichroism, atomic force microscopy, molecular
dynamics simulations, and a new thermodynamic method, transient equilibrium
mapping, elucidated the molecular factors behind these large changes.
In particular, we identify substantial DNA sugar and phosphate group
deformations to accommodate a hydrogen bond between the phosphate
and the small-molecule functional groups, as well as a critical chain
length of the functional group which switches this interaction from
intra- to interfiber. These parameters allow the controlled formation
of hierarchical, hybrid DNA assemblies simply through the addition
and variation of small, functionalized molecules.