The poly dA helix: a new structural motif for high performance DNA-based molecular switches

Abstract

We report a pH-dependent conformational transition in short, defined homopolymeric deoxyadenosines (dA15) from a single helical structure with stacked nucleobases at neutral pH to a double-helical, parallel-stranded duplex held together by AH+-H+A base pairs at acidic pH. Using native PAGE, 2D NMR, circular dichroism (CD) and fluorescence spectroscopy, we have characterized the two different pH dependent forms of dA15. The pH-triggered transition between the two defined helical forms of dA15 is characterized by CD and fluorescence. The kinetics of this conformational switch is found to occur on a millisecond time scale. This robust, highly reversible, pH-induced transition between the two well-defined structured states of dA15 represents a new molecular building block for the construction of quick-response, pH-switchable architectures in structural DNA nanotechnology.

Parallel Polyadenine Duplex Formation at Low pH Facilitates DNA Conjugation onto Gold Nanoparticles

“…Parallel poly-A duplexes have been studied in terms of biophysical properties, 36, 37 structure, 32,33,38,39 and analytical applications. 35,[40][41][42] Most previous work on used pure adenine homopolymers.…”

Reprogramming the assembly of unmodified DNA with a small molecule

“…Under highly acidic conditions (pH 3), poly(A) strands (both in their RNA and DNA forms) have been reported to self--associate into parallel homoduplexes as a result of protonation of the adenine units 36,37,43,44 . We ascertained that CA--mediated assembly of d(A 15 ) under the conditions described above (pH 4.5) is distinct from the pH--driven poly(A) duplex, based on major differences between the CD spectra of these species.…”

“…In the presence of poly(thymine), poly(adenine) can form double and triple helices. On its own, poly(adenine) can form a parallel homoduplex in acidic conditions, 36,37 whereas an antiparallel homoduplex can be formed at neutral pH with the addition of small molecule intercalators such as coralyne 30,31 . In principle, we can reprogram poly(adenine) interactions to induce assembly of a higher--order structure if we combine adenine with a small symmetric molecule such as cyanuric acid, that contains three complementary thymine--like faces (Fig.…”

DNA Nanobiosensors: An Outlook on Signal Readout Strategies

“…Such stem-loop configurations can also be used to monitor global environmental changes such as changes in temperature by using a fluorophore-quencher pair on the ends of the strands. Biosensors for other stimuli such as pH changes are based on structures that involve triplex [17] (Figure 1(c)), i-motif formation [18] (Figure 1(d)), or poly-dA helix formation (Figure 1(e)) [19], all of which are 2 Journal of Nanomaterials sequence-specific and occur under acidic conditions. Gquadruplex formation is another sequence-specific conformational change that forms under specific ionic conditions such as the presence of K + or Na + [20] (Figure 1(f)).…”