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710 KiB

Open AccessArticle

Addition of Bases to the 5'-end of Human Telomeric DNA: Influences on Thermal Stability and Energetics of Unfolding

by Katherine L. Hayden and David E. Graves

Molecules 2014, 19(2), 2286-2298; https://doi.org/10.3390/molecules19022286 - 21 Feb 2014

Cited by 7 | Viewed by 6865

Abstract

Telomeric DNA has been intensely investigated for its role in chromosome protection, aging, cell death, and disease. In humans the telomeric tandem repeat (TTAGGG)_n is found at the ends of chromosomes and provides a novel target for the development of new drugs [...] Read more.

Telomeric DNA has been intensely investigated for its role in chromosome protection, aging, cell death, and disease. In humans the telomeric tandem repeat (TTAGGG)_n is found at the ends of chromosomes and provides a novel target for the development of new drugs in the treatment of age related diseases such as cancer. These telomeric sequences show slight sequence variations from species to species; however, each contains repeats of 3 to 4 guanines allowing the G-rich strands to fold into compact and stable nuclease resistant conformations referred to as G-quadruplexes. The focus of this manuscript is to examine the effects of 5'-nucleotides flanking the human telomeric core sequence 5'-AGGG(TTAGGG) ₃-3' (h-Tel22). Our studies reveal that the addition of the 5'-flanking nucleotides (5'-T, and 5'-TT) results in significant changes to the thermodynamic stability of the G-quadruplex structure. Our data indicate that the observed changes in stability are associated with changes in the number of bound waters resulting from the addition of 5'-flanking nucleotides to the h-Tel22 sequence as well as possible intermolecular interactions of the 5' overhang with the core structure. Full article

(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)

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321 KiB

Open AccessArticle

The Human Telomere Sequence, (TTAGGG)₄, in the Absence and Presence of Cosolutes: A Spectroscopic Investigation

by Vishal R. Sharma and Richard D. Sheardy

Molecules 2014, 19(1), 595-608; https://doi.org/10.3390/molecules19010595 - 6 Jan 2014

Cited by 8 | Viewed by 6641

Abstract

Historically, biophysical studies of nucleic acids have been carried out under near ideal conditions, i.e., low buffer concentration (e.g., 10 mM phosphate), pH 7, low ionic strength (e.g., 100 mM) and, for optical studies, low concentrations of DNA (e.g., 1 × 10 [...] Read more.

Historically, biophysical studies of nucleic acids have been carried out under near ideal conditions, i.e., low buffer concentration (e.g., 10 mM phosphate), pH 7, low ionic strength (e.g., 100 mM) and, for optical studies, low concentrations of DNA (e.g., 1 × 10⁻⁶ M). Although valuable structural and thermodynamic data have come out of these studies, the conditions, for the most, part, are inadequate to simulate realistic cellular conditions. The increasing interest in studying biomolecules under more cellular-like conditions prompted us to investigate the effect of osmotic stress on the structural and thermodynamic properties of DNA oligomers containing the human telomere sequence (TTAGGG). Here, we report the characterization of (TTAGGG)₄ in potassium phosphate buffer with increasing percent PEG (polyethylene glycol) or acetonitrile. In general, the presence of these cosolutes induces a conformational change from a unimolecular hybrid structure to a multimolecular parallel stranded structure. Hence, the structural change is accompanied with a change in the molecularity of quadruplex formation. Full article

(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)

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1752 KiB

Open AccessArticle

G-Quadruplex Guanosine Gels and Single Walled Carbon Nanotubes

by Yuehua Yu, Victor L. Pushparaj, Omkaram Nalamasu and Linda B. McGown

Molecules 2013, 18(12), 15434-15447; https://doi.org/10.3390/molecules181215434 - 11 Dec 2013

Cited by 8 | Viewed by 6127

Abstract

Solubilization of single walled carbon nanotubes (SWNTs) in aqueous gel phases formed by reversible, G-quadruplex self-assembly of guanosine monophosphate (GMP) alone or with guanosine (Guo) is described. Unlike other media and methods for aqueous solubilization of SWNTs, the guanosine gels (“G-gels”) are found [...] Read more.

Solubilization of single walled carbon nanotubes (SWNTs) in aqueous gel phases formed by reversible, G-quadruplex self-assembly of guanosine monophosphate (GMP) alone or with guanosine (Guo) is described. Unlike other media and methods for aqueous solubilization of SWNTs, the guanosine gels (“G-gels”) are found to readily disperse high (>mg/mL) concentrations of individual rather than bundled SWNTs. SWNT dispersions in GMP alone precipitate in several hours and re-form upon shaking; however, dispersions in the binary GMP/Guo gels are indefinitely stable. Increasing GMP or KCl concentration in the binary gels increased the relative abundance of large diameter and semi-conducting SWNTs. Different gel compositions also displayed different selectivities toward SWNTs of different chiralities. These results indicate a strong connection between the self-assembled G-gels and the dimensions and structures of the SWNTs that they solubilize. Full article

(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)

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742 KiB

Open AccessArticle

Helping Eve Overcome ADAM: G-Quadruplexes in the ADAM-15 Promoter as New Molecular Targets for Breast Cancer Therapeutics

by Robert V. Brown, Vanessa C. Gaerig, Taesha Simmons and Tracy A. Brooks

Molecules 2013, 18(12), 15019-15034; https://doi.org/10.3390/molecules181215019 - 5 Dec 2013

Cited by 7 | Viewed by 5385

Abstract

ADAM-15, with known zymogen, secretase, and disintegrin activities, is a catalytically active member of the ADAM family normally expressed in early embryonic development and aberrantly expressed in various cancers, including breast, prostate and lung. ADAM-15 promotes extracellular shedding of E-cadherin, a soluble ligand [...] Read more.

ADAM-15, with known zymogen, secretase, and disintegrin activities, is a catalytically active member of the ADAM family normally expressed in early embryonic development and aberrantly expressed in various cancers, including breast, prostate and lung. ADAM-15 promotes extracellular shedding of E-cadherin, a soluble ligand for the HER2/neu receptor, leading to activation, increased motility, and proliferation. Targeted downregulation of both ADAM-15 and HER2/neu function synergistically kills breast cancer cells, but to date there are no therapeutic options for decreasing ADAM-15 function or expression. In this vein, we have examined a unique string of guanine-rich DNA within the critical core promoter of ADAM-15. This region of DNA consists of seven contiguous runs of three or more consecutive guanines, which, under superhelical stress, can relax from duplex DNA to form an intrastrand secondary G-quadruplex (G4) structure. Using biophysical and biological techniques, we have examined the G4 formation within the entire and various truncated regions of the ADAM-15 promoter, and demonstrate strong intrastrand G4 formation serving to function as a biological silencer element. Characterization of the predominant G4 species formed within the ADAM-15 promoter will allow for specific drug targeting and stabilization, and the further development of novel, targeted therapeutics. Full article

(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)

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831 KiB

Open AccessArticle

Targeting C-myc G-Quadruplex: Dual Recognition by Aminosugar-Bisbenzimidazoles with Varying Linker Lengths

by Nihar Ranjan and Dev P. Arya

Molecules 2013, 18(11), 14228-14240; https://doi.org/10.3390/molecules181114228 - 18 Nov 2013

Cited by 35 | Viewed by 6729

Abstract

G-quadruplexes are therapeutically important biological targets. In this report, we present biophysical studies of neomycin-Hoechst 33258 conjugates binding to a G-quadruplex derived from the C-myc promoter sequence. Our studies indicate that conjugation of neomycin to a G-quadruplex binder, Hoechst 33258, enhances its [...] Read more.

G-quadruplexes are therapeutically important biological targets. In this report, we present biophysical studies of neomycin-Hoechst 33258 conjugates binding to a G-quadruplex derived from the C-myc promoter sequence. Our studies indicate that conjugation of neomycin to a G-quadruplex binder, Hoechst 33258, enhances its binding. The enhancement in G-quadruplex binding of these conjugates varies with the length and composition of the linkers joining the neomycin and Hoechst 33258 units. Full article

(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)

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1736 KiB

Open AccessArticle

Selective G-Quadruplex DNA Recognition by a New Class of Designed Cyanines

by Rupesh Nanjunda, Eric A. Owens, Leah Mickelson, Tyler L. Dost, Ekaterina M. Stroeva, Hang T. Huynh, Markus W. Germann, Maged M. Henary and W. David Wilson

Molecules 2013, 18(11), 13588-13607; https://doi.org/10.3390/molecules181113588 - 4 Nov 2013

Cited by 26 | Viewed by 8007

Abstract

A variety of cyanines provide versatile and sensitive agents acting as DNA stains and sensors and have been structurally modified to bind in the DNA minor groove in a sequence dependent manner. Similarly, we are developing a new set of cyanines that have [...] Read more.

A variety of cyanines provide versatile and sensitive agents acting as DNA stains and sensors and have been structurally modified to bind in the DNA minor groove in a sequence dependent manner. Similarly, we are developing a new set of cyanines that have been designed to achieve highly selective binding to DNA G-quadruplexes with much weaker binding to DNA duplexes. A systematic set of structurally analogous trimethine cyanines has been synthesized and evaluated for quadruplex targeting. The results reveal that elevated quadruplex binding and specificity are highly sensitive to the polymethine chain length, heterocyclic structure and intrinsic charge of the compound. Biophysical experiments show that the compounds display significant selectivity for quadruplex binding with a higher preference for parallel stranded quadruplexes, such as cMYC. NMR studies revealed the primary binding through an end-stacking mode and SPR studies showed the strongest compounds have primary K_D values below 100 nM that are nearly 100-fold weaker for duplexes. The high selectivity of these newly designed trimethine cyanines for quadruplexes as well as their ability to discriminate between different quadruplexes are extremely promising features to develop them as novel probes for targeting quadruplexes in vivo. Full article

(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)

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798 KiB

Open AccessArticle

Xanthene and Xanthone Derivatives as G-Quadruplex Stabilizing Ligands

by Alessandro Altieri, Antonello Alvino, Stephan Ohnmacht, Giancarlo Ortaggi, Stephen Neidle, Daniele Nocioni, Marco Franceschin and Armandodoriano Bianco

Molecules 2013, 18(11), 13446-13470; https://doi.org/10.3390/molecules181113446 - 30 Oct 2013

Cited by 16 | Viewed by 8038

Abstract

Following previous studies on anthraquinone and acridine-based G-quadruplex ligands, here we present a study of similar aromatic cores, with the specific aim of increasing G-quadruplex binding and selectivity with respect to duplex DNA. Synthesized compounds include two and three-side chain xanthone and xanthene [...] Read more.

Following previous studies on anthraquinone and acridine-based G-quadruplex ligands, here we present a study of similar aromatic cores, with the specific aim of increasing G-quadruplex binding and selectivity with respect to duplex DNA. Synthesized compounds include two and three-side chain xanthone and xanthene derivatives, as well as a dimeric “bridged” form. ESI and FRET measurements suggest that all the studied molecules are good G-quadruplex ligands, both at telomeres and on G-quadruplex forming sequences of oncogene promoters. The dimeric compound and the three-side chain xanthone derivative have been shown to represent the best compounds emerging from the different series of ligands presented here, having also high selectivity for G-quadruplex structures with respect to duplex DNA. Molecular modeling simulations are in broad agreement with the experimental data. Full article

(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)

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423 KiB

Open AccessArticle

The Effect of Molecular Crowding on the Stability of Human c-MYC Promoter Sequence I-Motif at Neutral pH

by Jingjing Cui, Phillip Waltman, Vu H. Le and Edwin A. Lewis

Molecules 2013, 18(10), 12751-12767; https://doi.org/10.3390/molecules181012751 - 15 Oct 2013

Cited by 93 | Viewed by 10684

Abstract

We have previously shown that c-MYC promoter sequences can form stable i-motifs in acidic solution (pH 4.5–5.5). In terms of drug targeting, the question is whether c-MYC promoter sequence i-motifs will exist in the nucleus at neutral pH. In this work, we have [...] Read more.

We have previously shown that c-MYC promoter sequences can form stable i-motifs in acidic solution (pH 4.5–5.5). In terms of drug targeting, the question is whether c-MYC promoter sequence i-motifs will exist in the nucleus at neutral pH. In this work, we have investigated the stability of a mutant c-MYC i-motif in solutions containing a molecular crowding agent. The crowded nuclear environment was modeled by the addition of up to 40% w/w polyethylene glycols having molecular weights up to 12,000 g/mol. CD and DSC were used to establish the presence and stability of c-MYC i-motifs in buffer solutions over the pH range 4 to 7. We have shown that the c-MYC i-motif can exist as a stable structure at pH values as high as 6.7 in crowded solutions. Generic dielectric constant effects, e.g., a shift in the pKa of cytosine by more than 2 units (e.g., 4.8 to 7.0), or the formation of non-specific PEG/DNA complexes appear to contribute insignificantly to i-motif stabilization. Molecular crowding, largely an excluded volume effect of added PEG, having a molecular weight in excess of 1,000 g/mol, appears to be responsible for stabilizing the more compact i-motif over the random coil at higher pH values. Full article

(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)

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2354 KiB

Open AccessArticle

Identification of New Natural DNA G-Quadruplex Binders Selected by a Structure-Based Virtual Screening Approach

by Anna Artese, Giosuè Costa, Francesco Ortuso, Lucia Parrotta and Stefano Alcaro

Molecules 2013, 18(10), 12051-12070; https://doi.org/10.3390/molecules181012051 - 30 Sep 2013

Cited by 23 | Viewed by 6850

Abstract

The G-quadruplex DNA structures are mainly present at the terminal portion of telomeres and can be stabilized by ligands able to recognize them in a specific manner. The recognition process is usually related to the inhibition of the enzyme telomerase indirectly involved and [...] Read more.

The G-quadruplex DNA structures are mainly present at the terminal portion of telomeres and can be stabilized by ligands able to recognize them in a specific manner. The recognition process is usually related to the inhibition of the enzyme telomerase indirectly involved and over-expressed in a high percentage of human tumors. There are several ligands, characterized by different chemical structures, already reported in the literature for their ability to bind and stabilize the G-quadruplex structures. Using the structural and biological information available on these structures; we performed a high throughput in silico screening of commercially natural compounds databases by means of a structure-based approach followed by docking experiments against the human telomeric sequence d[AG₃(T₂AG₃)₃]. We identified 12 best hits characterized by different chemical scaffolds and conformational and physicochemical properties. All of them were associated to an improved theoretical binding affinity with respect to that of known selective G-binders. Among these hits there is a chalcone derivative; structurally very similar to the polyphenol butein; known to remarkably inhibit the telomerase activity. Full article

(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)

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357 KiB

Open AccessArticle

Macrocyclic Pyridyl Polyoxazoles: Structure-Activity Studies of the Aminoalkyl Side-Chain on G-Quadruplex Stabilization and Cytotoxic Activity

by Gifty Blankson, Suzanne G. Rzuczek, Cody Bishop, Daniel S. Pilch, Angela Liu, Leroy Liu, Edmond J. LaVoie and Joseph E. Rice

Molecules 2013, 18(10), 11938-11963; https://doi.org/10.3390/molecules181011938 - 26 Sep 2013

Cited by 7 | Viewed by 7017

Abstract

Pyridyl polyoxazoles are 24-membered macrocyclic lactams comprised of a pyridine, four oxazoles and a phenyl ring. A derivative having a 2-(dimethylamino)ethyl chain attached to the 5-position of the phenyl ring was recently identified as a selective G-quadruplex stabilizer with excellent cytotoxic activity, and [...] Read more.

Pyridyl polyoxazoles are 24-membered macrocyclic lactams comprised of a pyridine, four oxazoles and a phenyl ring. A derivative having a 2-(dimethylamino)ethyl chain attached to the 5-position of the phenyl ring was recently identified as a selective G-quadruplex stabilizer with excellent cytotoxic activity, and good in vivo anticancer activity against a human breast cancer xenograft in mice. Here we detail the synthesis of eight new dimethylamino-substituted pyridyl polyoxazoles in which the point of attachment to the macrocycle, as well as the distance between the amine and the macrocycle are varied. Each compound was evaluated for selective G-quadruplex stabilization and cytotoxic activity. The more active analogs have the amine either directly attached to, or separated from the phenyl ring by two methylene groups. There is a correlation between those macrocycles that are effective ligands for the stabilization of G-quadruplex DNA (DT_tran 15.5–24.6 °C) and cytotoxicity as observed in the human tumor cell lines, RPMI 8402 (IC₅₀ 0.06–0.50 μM) and KB3-1 (IC₅₀ 0.03–0.07 μM). These are highly selective G-quadruplex stabilizers, which should prove especially useful for evaluating both in vitro and in vivo mechanism(s) of biological activity associated with G-quaqdruplex ligands. Full article

(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)

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981 KiB

Open AccessArticle

A Highly Sensitive Telomerase Activity Assay that Eliminates False-Negative Results Caused by PCR Inhibitors

by Hidenobu Yaku, Takashi Murashima, Daisuke Miyoshi and Naoki Sugimoto

Molecules 2013, 18(10), 11751-11767; https://doi.org/10.3390/molecules181011751 - 25 Sep 2013

Cited by 9 | Viewed by 9385

Abstract

An assay for telomerase activity based on asymmetric polymerase chain reaction (A-PCR) on magnetic beads (MBs) and subsequent application of cycling probe technology (CPT) is described. In this assay, the telomerase reaction products are immobilized on MBs, which are then washed to remove [...] Read more.

An assay for telomerase activity based on asymmetric polymerase chain reaction (A-PCR) on magnetic beads (MBs) and subsequent application of cycling probe technology (CPT) is described. In this assay, the telomerase reaction products are immobilized on MBs, which are then washed to remove PCR inhibitors that are commonly found in clinical samples. The guanine-rich sequences (5'-(TTAGGG)n-3') of the telomerase reaction products are then preferentially amplified by A-PCR, and the amplified products are subsequently detected via CPT, where a probe RNA with a fluorophore at the 5' end and a quencher at the 3' end is hydrolyzed by RNase H in the presence of the target DNA. The catalyst-mediated cleavage of the probe RNA enhances fluorescence from the 5' end of the probe. The assay allowed us to successfully detect HeLa cells selectively over normal human dermal fibroblast (NHDF) cells. Importantly, this selectivity produced identical results with regard to detection of HeLa cells in the absence and presence of excess NHDF cells; therefore, this assay can be used for practical clinical applications. The lower limit of detection for HeLa cells was 50 cells, which is lower than that achieved with a conventional telomeric repeat amplification protocol assay. Our assay also eliminated false-negative results caused by PCR inhibitors. Furthermore, we show that this assay is appropriate for screening among G-quadruplex ligands to find those that inhibit telomerase activity. Full article

(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)

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Review

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684 KiB

Open AccessReview

G-Quadruplexes as Sensing Probes

by Branislav Ruttkay-Nedecky, Jiri Kudr, Lukas Nejdl, Darina Maskova, Rene Kizek and Vojtech Adam

Molecules 2013, 18(12), 14760-14779; https://doi.org/10.3390/molecules181214760 - 28 Nov 2013

Cited by 81 | Viewed by 11204

Abstract

Guanine-rich sequences of DNA are able to create tetrastranded structures known as G-quadruplexes; they are formed by the stacking of planar G-quartets composed of four guanines paired by Hoogsteen hydrogen bonding. G-quadruplexes act as ligands for metal ions and aptamers for various molecules. [...] Read more.

Guanine-rich sequences of DNA are able to create tetrastranded structures known as G-quadruplexes; they are formed by the stacking of planar G-quartets composed of four guanines paired by Hoogsteen hydrogen bonding. G-quadruplexes act as ligands for metal ions and aptamers for various molecules. Interestingly, the G-quadruplexes form a complex with anionic porphyrin hemin and exhibit peroxidase-like activity. This review focuses on overview of sensing techniques based on G-quadruplex complexes with anionic porphyrins for detection of various analytes, including metal ions such as K⁺, Ca²⁺, Ag⁺, Hg²⁺, Cu²⁺, Pb²⁺, Sr²⁺, organic molecules, nucleic acids, and proteins. Principles of G-quadruplex-based detection methods involve DNA conformational change caused by the presence of analyte which leads to a decrease or an increase in peroxidase activity, fluorescence, or electrochemical signal of the used probe. The advantages of various detection techniques are also discussed. Full article

(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)

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1527 KiB

Open AccessReview

Effect of Pressure on Thermal Stability of G-Quadruplex DNA and Double-Stranded DNA Structures

by Shuntaro Takahashi and Naoki Sugimoto

Molecules 2013, 18(11), 13297-13319; https://doi.org/10.3390/molecules181113297 - 29 Oct 2013

Cited by 43 | Viewed by 7997

Abstract

Pressure is a thermodynamic parameter that can induce structural changes in biomolecules due to a volumetric decrease. Although most proteins are denatured by pressure over 100 MPa because they have the large cavities inside their structures, the double-stranded structure of DNA is stabilized [...] Read more.

Pressure is a thermodynamic parameter that can induce structural changes in biomolecules due to a volumetric decrease. Although most proteins are denatured by pressure over 100 MPa because they have the large cavities inside their structures, the double-stranded structure of DNA is stabilized or destabilized only marginally depending on the sequence and salt conditions. The thermal stability of the G-quadruplex DNA structure, an important non-canonical structure that likely impacts gene expression in cells, remarkably decreases with increasing pressure. Volumetric analysis revealed that human telomeric DNA changed by more than 50 cm³ mol⁻¹ during the transition from a random coil to a quadruplex form. This value is approximately ten times larger than that for duplex DNA under similar conditions. The volumetric analysis also suggested that the formation of G-quadruplex DNA involves significant hydration changes. The presence of a cosolute such as poly(ethylene glycol) largely repressed the pressure effect on the stability of G-quadruplex due to alteration in stabilities of the interactions with hydrating water. This review discusses the importance of local perturbations of pressure on DNA structures involved in regulation of gene expression and highlights the potential for application of high-pressure chemistry in nucleic acid-based nanotechnology. Full article

(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)

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1219 KiB

Open AccessReview

G-Quadruplex Structures in the Human Genome as Novel Therapeutic Targets

by Joanna Bidzinska, Graziella Cimino-Reale, Nadia Zaffaroni and Marco Folini

Molecules 2013, 18(10), 12368-12395; https://doi.org/10.3390/molecules181012368 - 8 Oct 2013

Cited by 130 | Viewed by 12176

Abstract

G-quadruplexes are secondary structures that may form within guanine-rich nucleic acid sequences. Telomeres have received much attention in this regard since they can fold into several distinct intramolecular G-quadruplexes, leading to the rational design and development of G-quadruplex‑stabilizing molecules. These ligands were shown [...] Read more.

G-quadruplexes are secondary structures that may form within guanine-rich nucleic acid sequences. Telomeres have received much attention in this regard since they can fold into several distinct intramolecular G-quadruplexes, leading to the rational design and development of G-quadruplex‑stabilizing molecules. These ligands were shown to selectively exert an antiproliferative and chemosensitizing activity in in vitro and in vivo tumor models, without appreciably affecting normal cells. Such findings point to them as possible drug candidates for clinical applications. Other than in telomeres, G-quadruplexes may form at additional locations in the human genome, including gene promoters and untranslated regions. For instance, stabilization of G-quadruplex structures within the promoter of MYC, KIT, or KRAS resulted in the down-regulation of the corresponding oncogene either in gene reporter assays or in selected experimental models. In addition, the alternative splicing of a number of genes may be affected for a therapeutic benefit through the stabilization of G-quadruplexes located within pre-mRNAs. It is now emerging that G-quadruplex structures may act as key regulators of several biological processes. Consequently, they are considered as attractive targets for broad-spectrum anticancer therapies, and much effort is being made to develop a variety of ligands with improved G-quadruplex recognition properties. Quarfloxin, a fluoroquinolone derivative designed to target a G-quadruplex within ribosomal DNA and disrupt protein-DNA interactions, has entered clinical trials for different malignancies. This review will provide some hints on the role of G-quadruplex structures in biological processes and will evaluate their implications as novel therapeutic targets. Full article

(This article belongs to the Special Issue G-Quadruplexes & i-Motif DNA)

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