Abstract

Applications of nucleic acid nanotechnology have been expanding since the early 1980s. The specific sequence programmability of these macromolecules makes them an attractive candidate for self-assembled nanostructures. Since the discovery of the DNA double helix, numerous secondary structures have been reported including G-quadruplexes, triplexes and i-motifs which have all been investigated as a molecular switch responsive to an external stimuli that causes a conformational change. In 1961 Rich et al. described the structure of the polyadenylic acid duplex from the X-ray diffraction pattern of fibers. The structure was proposed to be a parallel stranded duplex which is stabilized by adenine-adenine base pairing. The duplex requires acidic conditions to form which emphasizes its suitability and attractiveness as a pH dependent nanoswitch. Modification of the nucleoside residues in the polyadenosine duplex may prove useful in increasing the functionality and stability of this structure. To examine this, oligoadenylates were synthesized with various modified nucleotides and their effect on adenosine duplex stability was evaluated by UV thermal denaturation studies. It has been observed that the substitution of adenosine (rA) with 2’-deoxyadenosine (dA) residues destabilize the rA duplex by ~8 °C/insert. 2’-Deoxy-2’-fluoroadenosine modifications (rfA) introduced into oligoadenylates have a destabilizing effect on duplex stability, however contrastingly to dA oligonucleotides the uniformly rfA strands are capable of hybridization. CD, NMR spectroscopy and crystallographic studies show minimal structural perturbations introduced by chemically modified nucleotides. The environmental requirement coupled with the ability to fine tune the stability or existence of adenine-adenine base pairs based on a simple modification at the 2’ position presents a novel construct for potential nanodevices.