Input-Dependent Induction of Oligonucleotide Structural Motifs for Performing Molecular Logic

Abstract

The K+–H+-triggered structural conversion of multiple nucleic acid helices involving duplexes, triplexes, G-quadruplexes, and i-motifs is studied by gel electrophoresis, circular dichroism, and thermal denaturation. We employ the structural interconversions for perfoming molecular logic operations, as verified by fluorimetry and colorimetry. Short G-rich and C-rich cDNA and RNA single strands are hybridized to produce four A-form and B-form duplexes. Addition of K+ triggers the unwinding of the duplexes by inducing the folding of G-rich strands into DNA- or RNA G-quadruplex mono- and multimers, respectively. We found a decrease in pH to have different consequences on the resulting structural output, depending on whether the C-rich strand is DNA or RNA: while the protonated C-rich DNA strand folds into at least two isomers of a stable i-motif structure, the protonated C-rich RNA strand binds a DNA/RNA hybrid duplex to form a Y·RY parallel triplex. When using K+ and H+ as external stimuli, or inputs, and the induced G-quadruplexes as reporters, these structural interconversions of nucleic acid helices can be employed for performing logic-gate operations. The signaling mode for detecting these conversions relies on complex formation between DNA or RNA G-quadruplexes (G4) and the cofactor hemin. The G4/hemin complexes catalyze the H2O2-mediated oxidation of peroxidase substrates, resulting in a fluorescence or color change. Depending on the nature of the respective peroxidase substrate, distinct output signals can be generated, allowing one to operate multiple logic gates such as NOR, INH, or AND.

Rational Design of pH-Controlled DNA Strand Displacement

“…A similar pH dependence has been observed with the clamp-like strands of strategy #2 ( Figure SI3). We also note that at acidic pH the possible alternative i-motif 21 that the triplex-forming strand (in Figure 1: c**b**) could form does not affect the pH dependence of our system. These results demonstrate that the clamp-like triplex formation based on Hoogsteen interactions offers highly efficient and tunable pH regulation, which could be suitable toward the realization of pH-dependent DNA-based molecular devices.…”

Regulation of Oncogene Expression via Targeting i-Motif in Nucleic Acids

“…The bcl2 i-Motif targeting compounds are IMC 48 and IMC 76 [9]. In addition, i-Motif structure has vast application in the field of nanotechnology, for example, as sensors to map pH changes in living cells [29,30], switches for logic operations [31][32][33], designing Nano machines [34,35] and assembly of gold nanoparticles.…”

A survey of advancements in nucleic acid-based logic gates and computing for applications in biotechnology and biomedicine

“…53–55 For example, mercury ions (Hg 2+ ) can interact with thymine-thymine (T-T) mismatch in DNA double strands, thus increasing the stability of the duplex. 41 A similar phenomenon also occurs between Ag + ion and cytosine-cytosine (C-C) mismatch.…”