Telomeric G-quadruplex Research Articles

Synergically Remodeling Human Telomeric G-Quadruplexes into DNA Mimics of GFP with a Na+ Selectivity.

DNA/RNA mimics of fluorescent proteins (DMFPs and RMFPs) have been exogenously screened for inspiring variant applications by specifically binding to chromophore analogues to activate their fluorescence. Considerable DMFPs and RMFPs form G-quadruplex (G4) or G4-like structures to accommodate FP chromophore analogues. Therefore, efforts ought to be made to investigate whether these FP chromophore analogues have distinctive interactions with endogenous G4 structures found in natural sequences, such as human telomeric G4s (htG4s). Herein, we found that htG4s can specifically interact with one of the hydroxyethylamino-benzylidene cyanophenyl chromophore derivatives (HBC514) to serve as DNA mimics of green FPs (DMGFPs). Importantly, Na+ is required to remodel the K+-favored hybrid htG4s into antiparallel htG4s-based DMGFPs with the synergic binding of HBC514. Furthermore, HBC514 most likely aggregates on DMGFPs into an AIEgen with suppressed intramolecular rotation to cause a 2 orders of magnitude enhancement in its fluorescence. Based on the Na+-specific DMGFPs, a selective Na+ sensor was developed with the potential to tolerate high K+ abundance using HBCs as the bifunctional G4-inducer and fluorescent reporter. The DMGFPs conquer the long-standing challenge of developing practical Na+ sensors that can be used in physiological environments (for example, serums) with a K+-instigated high G4 stability.

Cu2+-mediated telomeric dimeric G-quadruplex DNAzyme for highly sensitive colorimetric detection of deferasirox

Deferasirox (DEF) is an important iron chelator for treatment of iron overload–related diseases. Monitoring DEF concentration in human serum will provide some valuable information for clinical diagnosis and therapy of such diseases. In this study, we developed a peroxidase-mimicking colorimetric sensor for the detection of DEF by simple assembly of a telomeric dimeric G-quadruplex DNAzyme with Cu2+. The DNAzyme–catalyzed oxidation of 3,3′,5,5′-tetramethylbenzidine in the presence of H2O2 can generate a quantitative colorimetric signal, and the color change can be discerned by the naked eye. Compared with the reaction rate of the monomeric G-quadruplex–Cu2+ DNAzyme, the reaction rate of the dimeric G-quadruplex–Cu2+ (G2–Cu2+) DNAzyme is significantly accelerated, and the reaction rate gradually increases and then reaches a plateau with increasing number of TTA spacers. Herein, the G2–Cu2+ DNAzyme is chosen for the highly sensitive detection of DEF based on the DEF–Cu2+ complex–induced inhibition of its peroxidase-mimicking activities. The limit of detection (LOD) of DEF is achieved as low as 0.03 μM, and the linear range is from 0.05 to 1.2 μM. The proposed strategy exhibits excellent selectivity in the presence of potential interferents, such as metal ions and small molecules. Importantly, the G2–Cu2+ DNAzyme is further expanded to detect DEF in dispersible tablets and human serum samples. Overall, this G2–Cu2+ DNAzyme provides a simple, low-cost, and rapid platform for DEF detection. This novel strategy is the first example of DEF analysis by utilizing signal amplification technology based on the G-quadruplex DNAzyme and holds great potential for DEF quality control and therapeutic drug monitoring.

Rationally Designed G-Quadruplex Selective "Turn-On" NIR Fluorescent Probe with Large Stokes Shift for Nucleic Acid Research-Based Applications.

Guanine-rich DNA/RNA sequences can form Hoogsteen bonds to adopt noncanonical secondary structures called G-quadruplexes, and these have been associated with diverse cellular processes. There has been considerable research interest in the design of G4-interacting ligands for cellular probing of the G4 structure and understanding its associated biological function. Most of the fluorescent G4 ligands either do not have significant selectivity over other nucleic acid structures, have high Stokes shift, or are not in the near-infrared (NIR) region, which limits its cellular visualization. The current work involves the rational design and synthesis of NIR fluorescent probes comprising a (Z)-1-methyl-2-((3-methylbenzo[d]thiazol-2(3H)-ylidene)methyl)quinolin-1-ium scaffold. Among the designed molecules, 4a exhibited far-red fluorescence (λmax = 680 nm) with large Stokes shift (∼182 nm) upon selective binding to human telomeric G-quadruplexes. The dye 4a does not disturb the conformation and stability of G-quadruplexes, thereby making it suitable for nucleic acid research based applications. Interestingly, 4a showed remarkable selectivity over single- and double-stranded structures in contrast to a commercially available quadruplex binding probe, Thiazole orange (TO). The molecular docking studies indicate that 4a binds at the groove region of the telomeric DNA G-quadruplex through π-π stacking interactions with the quinoline and amine-substituted phenyl ring and with the phosphate backbone through anion-π interactions with the benzothiazole ring. The designed molecule 4a has interesting photophysical properties, cell permeability, and biocompatibility with minimal cytotoxicity. Fluorescence imaging studies in live HeLa cells showed that probe 4a binds to the transient population of the DNA G-quadruplex in the nucleus and RNA quadruplexes in the cytoplasm. In brief, G-quadruplex NIR fluorescent probe 4a with a higher signal/noise ratio has significant potential for cellular imaging studies and thus opens avenues to decipher the biological pathways for better understanding of G-quadruplex biology.

Human hnRNPA1 reorganizes telomere-bound replication protein A.

Human replication protein A (RPA) is a heterotrimeric ssDNA binding protein responsible for many aspects of cellular DNA metabolism. Dynamic interactions of the four RPA DNA binding domains (DBDs) with DNA control replacement of RPA by downstream proteins in various cellular metabolic pathways. RPA plays several important functions at telomeres where it binds to and melts telomeric G-quadruplexes, non-canonical DNA structures formed at the G-rich telomeric ssDNA overhangs. Here, we combine single-molecule total internal reflection fluorescence microscopy (smTIRFM) and mass photometry (MP) with biophysical and biochemical analyses to demonstrate that heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) specifically remodels RPA bound to telomeric ssDNA by dampening the RPA configurational dynamics and forming a ternary complex. Uniquely, among hnRNPA1 target RNAs, telomeric repeat-containing RNA (TERRA) is selectively capable of releasing hnRNPA1 from the RPA-telomeric DNA complex. We speculate that this telomere specific RPA-DNA-hnRNPA1 complex is an important structure in telomere protection.

Benzimidazole-based small molecules as anticancer agents targeting telomeric G-quadruplex and inhibiting telomerase enzyme.

Telomeres, crucial for chromosomal integrity, have been related to aging and cancer formation, mainly through regulating G-quadruplex structures. G-quadruplexes are structural motifs that can arise as secondary structures of nucleic acids, especially in guanine-rich DNA and RNA regions. Targeting these structures by small compounds shows promise in the selective suppression of cell growth, opening up novel possibilities for anticancer treatment. A comprehensive investigation of the many structural forms of G-quadruplex ligands is required to create ground-breaking anticancer drugs. Recent research into using specific benzimidazole molecules in stabilizing telomeric DNA into G-quadruplex structures has highlighted their ability to influence oncogene expression and demonstrate antiproliferative characteristics against cancer cells. This review describes the benzimidazole derivative, designed to enhance the stability of the G-quadruplex structure DNA to suppress the activity of telomerase enzyme, exhibiting promising potential for anticancer therapy.

Hindered intermolecular stacking of anti-parallel telomeric G-quadruplexes.

Telomeric G-quadruplexes (G4s) are non-canonical DNA structures composed of TTAGGG repeats. They are extensively studied both as biomolecules key for genome stability and as promising building blocks and functional elements in synthetic biology and nanotechnology. This is why it is extremely important to understand how the interaction between G4s is affected by their topology. We used small-angle x-ray scattering to investigate the end-to-end stacking of antiparallel telomeric G-quadruplexes formed by the sequence AG3(T2AG3)3. To represent the experimental data, we developed a highly efficient coarse-grained fitting tool, which successfully described the samples as an equilibrium mixture of monomeric and dimeric G4 species. Our findings indicate that the antiparallel topology prevents the formation of long multimeric structures under self-crowding conditions, unlike the hybrid/parallel structures formed by the same DNA sequence. This result supports the idea that the stacking of monomeric G-quadruplexes is strongly affected by the presence of diagonal loops.

Early Events in G-quadruplex Folding Captured by Time-Resolved Small-Angle X-Ray Scattering.

Time-resolved small-angle X-ray experiments (TR-SAXS) are reported here that capture and quantify a previously unknown rapid collapse of the unfolded oligonucleotide as an early step in G4 folding of hybrid 1 and hybrid 2 telomeric G-quadruplex structures. The rapid collapse, initiated by a pH jump, is characterized by an exponential decrease in the radius of gyration from 20.6 to 12.6 Å. The collapse is monophasic and is complete in less than 600 ms. Additional hand-mixing pH-jump kinetic studies show that slower kinetic steps follow the collapse. The folded and unfolded states at equilibrium were further characterized by SAXS studies and other biophysical tools, to show that G4 unfolding was complete at alkaline pH, but not in LiCl solution as is often claimed. The SAXS Ensemble Optimization Method (EOM) analysis reveals models of the unfolded state as a dynamic ensemble of flexible oligonucleotide chains with a variety of transient hairpin structures. These results suggest a G4 folding pathway in which a rapid collapse, analogous to molten globule formation seen in proteins, is followed by a confined conformational search within the collapsed particle to form the native contacts ultimately found in the stable folded form.

Synthesis and Molecular Dynamic Simulation of Novel Cationic and Non-cationic Pyrimidine Derivatives as Potential G-quadruplex-ligands.

Drug resistance has been a problem in cancer chemotherapy, which often causes shortterm effectiveness. Further, the literature indicates that telomere G-quadruplex could be a promising anti-cancer target. We synthesized and characterized two new pyrimidine derivatives as ligands for G-quadruplex DNA. The interaction of novel non-cationic and cationic pyrimidine derivatives (3a, b) with G-quadruplex DNA (1k8p and 3qsc) was explored by circular dichroism (CD) and ultraviolet-visible spectroscopy and polyacrylamide gel electrophoresis (PAGE) methods. The antiproliferative activity of desired compounds was evaluated by the MTT assay. Apoptosis induction was assessed by Propidium iodide (P.I.) staining and flow cytometry. Computational molecular modeling (CMM) and molecular dynamics simulation (MD) were studied on the complexes of 1k8p and 3qsc with the compounds. The van der Waals, electrostatic, polar solvation, solventaccessible surface area (SASA), and binding energies were calculated and analyzed. The experimental results confirmed that both compounds 3a and 3b interacted with 1k8p and 3qsc and exerted cytotoxic and proapoptotic effects on cancer cells. The number of hydrogen bonds and the RMSD values increased in the presence of the ligands, indicating stronger binding and suggesting increased structural dynamics. The electrostatic contribution to binding energy was higher for the cationic pyrimidine 3b, indicating more negative binding energies. Both experimental and MD results confirmed that 3b was more prone to form a complex with DNA G-quadruplex (1k8p and 3qsc), inhibit cell growth, and induce apoptosis, compared to the non-cationic pyrimidine 3a.

Structural and biochemical characterization of the C-terminal region of the human RTEL1 helicase.

RTEL1 is an essential DNA helicase which plays an important role in various aspects of genome stability, from telomere metabolism to DNA replication, repair and recombination. RTEL1 has been implicated in a number of genetic diseases and cancer development, including glioma, breast, lung and gastrointestinal tumors. RTEL1 is a FeS helicase but, in addition to the helicase core, it comprises a long C-terminal region which includes a number of folded domains connected by intrinsically disordered loops and mediates RTEL1 interaction with factors involved in pivotal cellular pathways. However, information on the architecture and the function of this region is still limited. We expressed and purified a variety of fragments encompassing the folded domains and the unstructured regions. We determined the crystal structure of the second repeat, confirming that it has a fold similar to the harmonin homology domains. SAXS data provide low-resolution information on all the fragments and suggest that the presence of the RING domain affects the overall architecture of the C-terminal region, making the structure significantly more compact. NMR data provide experimental information on the interaction between PCNA and the RTEL1 C-terminal region, revealing a putative low-affinity additional site of interaction. A biochemical analysis shows that the C-terminal region, in addition to a preference for telomeric RNA and DNA G-quadruplexes, has a high affinity for R-loops and D-loops, consistent with the role played by the RTEL1 helicase in homologous recombination, telomere maintenance and preventing replication-transcription conflicts. We further dissected the contribution of each domain in binding different substrates.

Unravelling the hydrogen bonding patterns in telomeric G-quadruplexes: from structure to function*

In this work, we investigate the molecular basis of the telomere model of ageing. Its key trait is the hydrogen (H–) bonding patterns of G-tetrads that serve a top of G-quadruplexes composing telomeres. We show that these patterns demonstrate a variety of bonding characters – from classic hydrogen bonds to so-called ‘over-coordinated oxygen (OCO)’ bifurcated H-bonds that thus result in non-rigidity of G-tetrad structures. This work has implications for the functionality of G-quadruplexes and, in turn, for the quadruplex-based telomere model of ageing.

Enhanced Recognition of a Herbal Compound Epiberberine by a DNA Quadruplex-Duplex Structure.

The small molecule epiberberine (EPI) is a natural alkaloid with versatile bioactivities against several diseases including cancer and bacterial infection. EPI can induce the formation of a unique binding pocket at the 5' side of a human telomeric G-quadruplex (HTG) sequence with four telomeric repeats (Q4), resulting in a nanomolar binding affinity (KD approximately 26 nM) with significant fluorescence enhancement upon binding. It is important to understand (1) how EPI binding affects HTG structural stability and (2) how enhanced EPI binding may be achieved through the engineering of the DNA binding pocket. In this work, the EPI-binding-induced HTG structure stabilization effect was probed by a peptide nucleic acid (PNA) invasion assay in combination with a series of biophysical techniques. We show that the PNA invasion-based method may be useful for the characterization of compounds binding to DNA (and RNA) structures under physiological conditions without the need to vary the solution temperature or buffer components, which are typically needed for structural stability characterization. Importantly, the combination of theoretical modeling and experimental quantification allows us to successfully engineer Q4 derivative Q4-ds-A by a simple extension of a duplex structure to Q4 at the 5' end. Q4-ds-A is an excellent EPI binder with a KD of 8 nM, with the binding enhancement achieved through the preformation of a binding pocket and a reduced dissociation rate. The tight binding of Q4 and Q4-ds-A with EPI allows us to develop a novel magnetic bead-based affinity purification system to effectively extract EPI from Rhizoma coptidis (Huang Lian) extracts.

Structural and biophysical insights into the interactions of anisotropic gold nanoparticles with human telomeric G-quadruplex DNA: Spectroscopic and calorimetric approach

We are reporting curcumin-induced synthesis of anisotropic citrate capped Gold nanoparticles (ctGNPs). The techniques such as UV–visible spectroscopy, Raman spectroscopy, FT-IR, X-ray diffraction (XRD), and Transmission Electron Microscopy (TEM) were used to characterize the nanoparticles. The synthetic route shows the formation of an anisotropic gold nanostructure consisting of spherical, triangles, hexagonals, and a low-yield rod with an aspect ratio ranging from 4.2 to 8.5. Curcumin-derived ctGNPs shows stability at different physiological conditions and better biocompatibility. Synthesized nanoparticles are found non-toxic towards eukaryotic cells but more effective against the cancer cell lines HeLa and MCF-7. The interaction of these synthesized nanoparticles with human telomeric G-quadruplex (GQ) DNA was studied using different physiochemical methods. The spectroscopic studies show that synthesized nanoparticles have stronger binding affinity towards telomeric GQ as compared to ds DNA through Van der Waals and H-bonding interactions. Thermodynamic interpretation reveals that the formation of the complex between the telomeric GQ and ctGNPs are enthalpy driven and entropy unfavourable process, resulting in motion freezing and, eventually, AuNP aggregation. Thus, our study shows a new approach to understand the interaction of telomeric G-quadruplexes with gold nanoparticles generated via the green route.

Flanking Effect on the Structure and Stability of Human Telomeric G-Quadruplex in Varying Salt Concentrations.

The stability of the human telomere G-quadruplex (G4) is directly linked to cancer disease. The human telomere is mostly associated with the flanking nucleobases, which can affect the stability of G4. Hence, in this study, the effect of the flanking nucleobases in the context of their chemical nature, number, and position on the structure and stability of G4 has been investigated in varying concentrations of KCl mimicking the normal and cancer KCl microenvironments. The addition of flanking nucleobases does not alter the G4 topology. However, the presence of merely a single flanking nucleobase destabilizes the telomeric G4. This destabilizing effect is more prominent for thymine than adenine flanking nucleobase, probably due to the formation of the intermolecular G4 topology by thymine. Interestingly, the change in the stability of the telomeric G4 in the presence of thymine flanking nucleobase is sensitive to the concentration of KCl relevant to the normal and cancerous microenvironments, in contrast to adenine. Flanking nucleobases have a greater impact at the 5' end compared to the 3' end, particularly noticeable in KCl concentrations resembling the normal microenvironment rather than the cancerous one. These findings indicate that the effect of the flanking nucleobases on telomeric G4 is different in the KCl salt relevant to normal and cancerous microenvironments. This study may be helpful in attaining molecular-level insight into the role of G4 in telomeric length regulation under normal and cancerous KCl salt conditions.

Curcumin Knoevenagel's Schiff Base as a Promising Stabilizer of G-Quadruplex Structure.

G-quadruplex DNA sequences present in the promoter and telomere regions of the genomic sequence are considered therapeutic targets for the treatment of cancer. Curcumin, derived from Curcuma longa, has been known as a quadruplex binder and has a potential role in the apoptosis of cancer cells. Here, we have reported the Schiff base ligand of curcumin synthesized through the condensation of the amino acid L-tryptophan and the knoevenagel derivative of curcumin (4-nitrobenzylidene curcumin (NBC)) as a potential G-quadruplex binder. Thus, spectroscopic and biophysical studies reveal a higher binding affinity of the ligand Sb-NBC towards the promoter and telomere G-quadruplex sequence as compared to the parent NBC. The ligand Sb-NBC highly stabilizes the parallel and hybrid G-quadruplex topologies to 10.5 °C-6.4 °C. Interestingly, the ligands also exhibit selective cytotoxicity toward cancer cells over normal cells. Taken together, this work provides evidence of the possibility of applying curcumin Schiff base in cancer therapy to regulate oncogene expression in cancer cells.

Development of a multi-targeted chemotherapeutic approach based on G-quadruplex stabilisation and carbonic anhydrase inhibition

A novel class of compounds designed to hit two anti-tumour targets, G-quadruplex structures and human carbonic anhydrases (hCAs) IX and XII is proposed. The induction/stabilisation of G-quadruplex structures by small molecules has emerged as an anticancer strategy, disrupting telomere maintenance and reducing oncogene expression. hCAs IX and XII are well-established anti-tumour targets, upregulated in many hypoxic tumours and contributing to metastasis. The ligands reported feature a berberine G-quadruplex stabiliser scaffold connected to a moiety inhibiting hCAs IX and XII. In vitro experiments showed that our compounds selectively stabilise G-quadruplex structures and inhibit hCAs IX and XII. The crystal structure of a telomeric G-quadruplex in complex with one of these ligands was obtained, shedding light on the ligand/target interaction mode. The most promising ligands showed significant cytotoxicity against CA IX-positive HeLa cancer cells in hypoxia, and the ability to stabilise G-quadruplexes within tumour cells.

Novel quinoxaline analogs as telomeric G-quadruplex ligands exert antitumor effects related to enhanced immunomodulation

G-quadruplexes (G4s) are commonly formed in the G-rich strand of telomeric DNA. Ligands targeting telomeric G4 induce DNA damage and telomere dysfunction, which makes them potential antitumor drugs. New telomeric G4 ligands with drug-likeness are still needed to be exploited, especially with their antitumor mechanisms thoroughly discussed. In this study, a novel series of quinoxaline analogs were rationally designed and synthesized. Among them, R1 was the most promising ligand for its cytotoxic effects on tumor cells and stabilizing ability with telomeric G4. Cellular assays illustrated that R1 stabilized G4 and induced R-loop accumulation in the telomeric regions, subsequently triggering DNA damage responses, cell cycle arrest in G2/M phase, apoptosis and antiproliferation. Moreover, R1 evoked immunogenic cell death (ICD) in tumor cells, which promoted the maturation of bone marrow derived dendritic cells (BMDCs). In breast cancer mouse model, R1 exhibited a significant decrease in tumor burden through the immunomodulatory effects, including the increase of CD4+ and CD8+ T cells in tumors and cytokine levels in sera. Our research provides a new idea that targeting telomeric G4 induces DNA damage responses, causing antitumor effects both in vitro and in vivo, partially due to the enhancement of immunomodulation.

Electrochemical genosensor based on RNA-responsive human telomeric G-quadruplex DNA: A proof-of-concept with SARS-CoV-2 RNA

In this report, a facile and label-free electrochemical RNA biosensor is developed by exploiting methylene blue (MB) as an electroactive positive ligand of G-quadruplex. The electrochemical response mechanism of the nucleic acid assay was based on the change in differential pulse voltammetry (DPV) signal of adsorbed MB on the immobilized human telomeric G-quadruplex DNA with a loop that is complementary to the target RNA. Hybridization between synthetic positive control RNA and G-quadruplex DNA probe on the transducer platform rendered a conformational change of G-quadruplex to double-stranded DNA (dsDNA), and increased the redox current of cationic MB π planar ligand at the sensing interface, thereby the electrochemical signal of the MB-adsorbed duplex is proportional to the concentration of target RNA, with SARS-CoV-2 (COVID-19) RNA as the model. Under optimal conditions, the target RNA can be detected in a linear range from 1 zM to 1 μM with a limit of detection (LOD) obtained at 0.59 zM for synthetic target RNA and as low as 1.4 copy number for positive control plasmid. This genosensor exhibited high selectivity towards SARS-CoV-2 RNA over other RNA nucleotides, such as SARS-CoV and MERS-CoV. The electrochemical RNA biosensor showed DPV signal, which was proportional to the 2019-nCoV_N_positive control plasmid from 2 to 200000 copies (R2 = 0.978). A good correlation between the genosensor and qRT-PCR gold standard was attained for the detection of SARS-CoV-2 RNA in terms of viral copy number in clinical samples from upper respiratory specimens.

Functional evaluation of novel chromon derivative compounds for recognition of G-quadruplex structure

Currently, G-quadruplex structure targeting strategies are considered as a promising anticancer approach. The purpose of this research is to expand the options for G-quadruplex targeting ligands, particularly emphasizing fluorescent ligands. Our study contributes to the field by providing additional choices for G-quadruplex binders with a notable focus on selectivity towards G-quadruplex topology over duplex DNA. In the search of selective and potent G-quadruplex binders, here we discuss an analysis of a few chroman derivatives ligands named A and C and their respective borondifluoride complexes B and D as a quadruplex targeting compounds which found to stabilize G-quadruplex structure. To investigate the binding characteristics of these molecules with G-quadruplex vs. duplex selectivity, In vitro biophysical studies were performed by steady-state fluorescence, UV–visible titration, fluorescent TO displacement assay, CD thermal melting, circular dichroism spectroscopy, and cellular imaging by employing both telomeric and PRCC G-quadruplex forming sequences. Our investigation shows that these chromam ligands and their complexes are able to selectively bind and stabilize parallel and mixed hybrid topology of G-quadruplex both In vitro and in cellular conditions. A molecular docking and MD simulation study also suggests the binding of these compounds with G-quadruplex conformation. Collectively our study suggests these chroman complexes for the first time as a potentially useful fluorescent chemical product for G-quadruplex specific ligands and expands an option for G-quadruplex targeting ligands.

Probing the binding and interaction of curcumin-tryptophan conjugate to G-quadruplex motif via spectroscopic and molecular docking approach

A potential ligand with the ability to interact with the structure of G-quadruplexes has been promising strategy for develop anticancer drug. Curcumin, a natural antioxidant is known to induce apoptosis in the tumour cells and was previously found as G-quadruplex binder. We investigated how the conjugation of tryptophan with curcumin affects its ability as G-quadruplex DNA binder. We have reported the differential interaction of Curcumin-tryptophan (CT) with a parallel G-quadruplex(GQ) formed by the nuclease hypersensitivity element (NHEIII) Pu27 present of the protooncogene and human telomeric G-quadruplex sequence. Taken into account, ligand CT has a stronger binding affinity for the G-quadruplex over the canonical duplex DNA. We have used biophysical approach such as uv-visible, fluorescence, circular dichroism, differential scanning calorimetry and molecular docking experiment to show that curcumin tryptophan interacts with the G-quadruplex. The results indicate that CT has a binding affinity of 106 M−1 for G-quadruplexes. Thermodynamic studies show that the ligand CT destabilizes the G-quadruplexes (6–8 °C) due to aromatic core stacking between the tetrad. The anti-proliferative experiment of the synthesized ligand CT in vitro on several cancer cell lines such as HeLa cells and MCF-7 cell lines shows that it is more effective against MCF-7. Thus, present studies report Curcumin-tryptophan as a potential G-quadruplex binder that destabilizes the quadruplex structure .

Characterization of the conformational binding of N-methyl mesoporphyrin IX using fluorescent model DNA telomeric G-quadruplex forming sequences

Characterization of the conformational binding of N-methyl mesoporphyrin IX using fluorescent model DNA telomeric G-quadruplex forming sequences