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DNA-tuned dye assemblies have received considerable attention toward developing various devices. Owing to easy conformation implementation, G-quadruplexes (G4s) have been extensively used as initiators to grow dye assemblies with controllable chiralities. However, programmed chirality regulation of dye assemblies for a given G4 sequence has not been realized in a straightforward manner. In this work, we replaced a middle guanine in the G-tracts of a human telomeric G4 with an apurinic site (AP site) to meet the programmed dye assemblies. Although all of the AP site replacements altered the G4 conformation from the hybrid to the antiparallel folding, the handedness of pinacyanol (PIN) assemblies grown on the AP site-containing G4 was programmably regulated. The G4 with the AP site at the 5′-most G-tract grew right-handed assemblies, while that with the AP site at the 3′-most G-tract grew left-handed assemblies. The handedness of assemblies almost totally mirrored each other within 450–700 nm. Interestingly, we found that the AP site provided a specific binding site for guanosine and guanine, and this binding event sensitively broke the chiral assemblies. Thus, dye assembly-based sensors can be easily established based on the chiral responses with a high selectivity and sensitivity. Our work first demonstrates the AP site programmed chirality regulation of G4-grown dye assemblies and will find wide application in chiral devices. [ABSTRACT FROM AUTHOR]

G-triplex (G3) has been recognized as a popular intermediate during the folding of G-quadruplex (G4). This has raised interest to anticipate the ultimate formation of G3 by shortening the G4-forming oligonucleotides with the remaining three G-tracts. Some G3 structures have been validated and their stability has been found to be affected by the loop sequences similar to G4s. In this work, however, we first found that an intermolecular parallel G4 structure was preferred in K+ for the oligonucleotide 5′-TGGGTAGGGCGGG-3′ (DZ3) containing only three G-tracts. We screened auramine O (AO) as the appropriate fluorophore with a molecular rotor feature to target this G4 structure. AO bound with DZ3 in a 1 : 4 ratio, as confirmed by isothermal titration calorimetry experiments, suggesting the formation of a tetramolecular G4 structure (4erG4). The excimer emission from the labelled pyrene and the DNA melting behavior at various pHs in the presence of Ag+ proved the formation of the 4erG4 structure rather than the prevalent intramolecular G3 folding. This work demonstrates that one should be cautious while putatively predicting a G3 structure from an oligonucleotide containing three G-tracts. [ABSTRACT FROM AUTHOR]

Depurination occurs via hydrolysis of the purine-deoxyribose glycosyl bond and causes nucleic acid damage. In particular, the DNA sequences that can undergo a self-catalyzed depurination (SCD) will cause a great uncertainty in duplicating, separating, purifying, and storing the DNA samples. Therefore, there is a great demand to develop a rapid detection method for SCD events. Herein, the use of a convenient fluorescence method to follow the site-specific SCD was demonstrated. We found that the resultant apurine site (AP site) from depurination can be selectively recognized by a fluorescent probe of palmatine (PAL) with a turn-on fluorescence response. The dependence of SCD on the bases of the depurination site, pH, metal ions, and time shows that our method can be used to rapidly evaluate the depurination process. Furthermore, the depurination process can be photo-switched using a photoacid as an external initiator. Our work will find wide applications in preliminarily identifying the DNA depurination. [ABSTRACT FROM AUTHOR]

Efficient structuring of DNA by small molecules is very crucial in developing DNA-based novel switches with an ideal performance. In this work, we found that inverting only the polarity of the 3′ terminal guanine of the thrombin-binding aptamer (3iTBA) totally eradicates the original TBA G-quadruplex (G4) structure in K+. The unstructured 3iTBA can be further refolded upon specifically interacting with small molecules of natural isoquinoline alkaloids (IAs) due to their fruitful binding patterns with variant nucleic acid structures. We identified that 3iTBA can serve as a topology selector for planar IAs. Nitidine (NIT), owing to the planar aromatic ring and coplanar substituents, is the most efficient to restructure the 3iTBA random coil toward the anti-parallel G4 conformation. However, common metal ions can't realize this structuring. The topology selector competency of 3iTBA toward IAs’ planarity can be visualized using gold nanoparticles (AuNPs) as the chromogenic readout. Our work expands the G4 repertoire by exploring the polarity inversion regulation and provides a new approach to switch nucleic acid structures toward a small molecule structure-sensitive sensor. [ABSTRACT FROM AUTHOR]

Human telomeric repeat-containing RNA (TERRA), which has recently been found to play as important a role in living cells as its DNA counterpart, solely adopts a parallel G-quadruplex (G4) topology. However, developing a highly selective fluorescent probe specific for the TERRA G4 is a great challenge, since difficulty arises in differentiating it from the DNA G4s that possess polymorphic structures including parallel, (3 + 1) hybrid, basket, and chair topologies. In this work, 5,10,15,20-tetrakis(3,5-dihydroxyphenyl)porphyrin (TOHdPP) was selected out of various porphyrins as the most efficient fluorescent probe in targeting TERRA. We found that only the TERRA binding is effective in activating the hyperporphyrin spectrum of TOHdPP, favoring red-shifted spectral bands and an enhanced fluorescence emission. Following the previous investigations on the TERRA G4 structure and our present experiments, we anticipate that TOHdPP most likely interacts with the 5′ tetrads of two TERRA G4s via a 1 : 2 sandwich association. The ribose 2′-OH favors the loop adenine residue-extended tetrad G4 plane that is specific for TERRA, thus besides π-stacking with the G4 tetrads, TOHdPP should also interact with this substructure to trigger an efficient electron communication between the tetraphenyl substituents and the porphyrin macrocycle, as required by the hyperporphyrin effect. The hydrogen bonding interactions of the eight hydroxyl substituents in TOHdPP with the backbone phosphate oxygen atoms of TERRA most likely further contribute to the binding selectivity. Our work demonstrates the potential of TOHdPP as a selective TERRA G4 fluorescent probe and a promising TERRA-based sensor reporter. [ABSTRACT FROM AUTHOR]