G-quadruplex Recognition Research Articles

G-Quadruplex Recognition by Tetraalkylammonium Ions: A New Paradigm for Discrimination between Parallel and Antiparallel G-Quadruplexes.

G-quadruplexes are an important class of noncanonical secondary structures of DNA that exist in the cell and are involved in the regulation of principal genomic events. Any regulatory role of a G-quadruplex in the genome is coupled with the attendant interconversions between the G-quadruplex and duplex states. Much effort has been invested in the quest for agents that can recognize individual G-quadruplexes and shift the associated duplex-G-quadruplex equilibria toward the G-quadruplex state. In this communication, we demonstrate that, notwithstanding their simplicity, tetraalkylammonium ions, [H(CH2)n]4N+, recognize and strongly stabilize the parallel c-MYC G-quadruplex, while not binding to the antiparallel human telomeric G-quadruplex or duplex DNA. The affinity of TAA+ ions for the c-MYC G-quadruplex correlates with the length of the aliphatic side chains. Our CD spectral data suggest that the binding of tetraalkylammonium ions is external, not resulting in structural changes in the host G-quadruplex. The observed discriminatory power identifies tetraalkylammonium salts as a starting point for developing topology-selective G-quadruplex-binding agents.

Unlocking the potential of protein-derived peptides to target G-quadruplex DNA: from recognition to anticancer activity.

Noncanonical nucleic acid structures, particularly G-quadruplexes, have garnered significant attention as potential therapeutic targets in cancer treatment. Here, the recognition of G-quadruplex DNA by peptides derived from the Rap1 protein is explored, with the aim of developing novel peptide-based G-quadruplex ligands with enhanced selectivity and anticancer activity. Biophysical techniques were employed to assess the interaction of a peptide derived from the G-quadruplex-binding domain of the protein with various biologically relevant G-quadruplex structures. Through alanine scanning mutagenesis, key amino acids crucial for G-quadruplex recognition were identified, leading to the discovery of two peptides with improved G-quadruplex-binding properties. However, despite their in vitro efficacy, these peptides showed limited cell penetration and anticancer activity. To overcome this challenge, cell-penetrating peptide (CPP)-conjugated derivatives were designed, some of which exhibited significant cytotoxic effects on cancer cells. Interestingly, selected CPP-conjugated peptides exerted potent anticancer activity across various tumour types via a G-quadruplex-dependent mechanism. These findings underscore the potential of peptide-based G-quadruplex ligands in cancer therapy and pave the way for the development of novel therapeutic strategies targeting these DNA structures.

A bichromophoric squaraine based NIR fluorescent probe for G-quadruplex in living cells

The polymorphic formation of G-quadruplex brings more attentions, because changes of formation sites affect many physiological processes, like telomere maintenance, transcription and DNA replication. These processes are highly susceptible to ROS-induced oxidative damage. In this work, bichromophoric cores of symmetric squaraine probe SQ linked with ether chain is conducive to the recognition of G-quadruplex, based on the mechanism of intra or intermolecular “aggregation-disaggregation”. Several interaction behaviors, such as self-aggregation, binding affinity, stoichiometric ratio, were fully investigated via spectrum titration, circular dichroism, fluorescent intercalator displacement assay, and molecular docking. Furthermore, tracking G-quadruplex distribution in the cytoplasm was monitored by SQ during the oxidative stress enhancement. Interestingly, the G-quadruplex levels in the cytoplasm of cancer cells were slightly higher than that of normal cells to deal with oxidation-reduction imbalance. Overall, the lower detection limit of SQ for parallel G-quadruplex like pu27 is as low as 7.2 nM; and the complex of SQ and G-quadruplex will not change the topological structure of G-quadruplex. It has good sensitive and stability for parallel type of G-quadruplex. It is a potential tool for bioimaging of G-quadruplex in the cytoplasm.

Selective Recognition of c-KIT 1 G-Quadruplex by Structural Tuning of Heteroaromatic Scaffolds and Side Chains.

In this study, carbazole (MC) and dibenzofuran (MD) derivatives were synthesized to examine their effect on the biomolecular recognition of G-quadruplex (G4) targets. Biophysical studies revealed that MC-4, a carbazole derivative, exhibits a specific affinity and effectively stabilizes the c-KIT 1 G4. Molecular modeling suggests a stable interaction of MC-4 with the terminal G-tetrad of c-KIT 1 G4. Biological studies demonstrate that MC-4 efficiently enters cells, reduces c-KIT gene expression, and induces cell cycle arrest, DNA damage, and apoptosis in cancer cells. These findings demonstrate MC-4 as a selective c-KIT G4 ligand with therapeutic potential, providing insight into the structural basis of its anticancer mechanisms.

The N-terminal region of Cdc6 specifically recognizes human DNA G-quadruplex

Guanine (G)-rich nucleic acid sequences can form diverse G-quadruplex structures located in functionally significant genome regions, exerting regulatory control over essential biological processes, including DNA replication in vivo. During the initiation of DNA replication, Cdc6 is recruited by the origin recognition complex (ORC) to target specific chromosomal DNA sequences. This study reveals that human Cdc6 interacts with G-quadruplex structure through a distinct region within the N-terminal intrinsically disordered region (IDR), encompassing residues 7–20. The binding region assumes a hook-type conformation, as elucidated by the NMR solution structure in complex with htel21T18. Significantly, mutagenesis and in vivo investigations confirm the highly specific nature of Cdc6's recognition of G-quadruplex. This research enhances our understanding of the fundamental mechanism governing the interaction between G-quadruplex and the N-terminal IDR region of Cdc6, shedding light on the intricate regulation of DNA replication processes.

Modular symmetric ligands for selective recognition of cancer-relevant G-quadruplexes

New G-quadruplex-interactive and selective ligands are strongly required to evolve innovative, effective and minimally toxic anticancer agents. With this purpose, we have here synthesized and evaluated a mini-library of organic molecules featured by aromatic cores of different rigidity (naphthalene or bioxazole), decorated with pendant groups including positively charged moieties and/or H-bond donors/acceptors. By exploiting different biophysical techniques, we proved the ability of the bioxazole-based derivatives to strongly and selectively interact with telomeric and oncogenic G-quadruplexes, while the compound featured by a naphthalene core did not emerge as a good G-quadruplex ligand. Molecular docking studies demonstrated the ability of the bioxazole-based ligands to preferentially target the outer G-tetrads of both telomeric and oncogenic G-quadruplexes, by positioning their cores on the G-tetrads in a symmetrical or asymmetrical way respectively, with the pendant groups pointing towards or away from the grooves. All bioxazole-based ligands showed anticancer activity in the low micromolar range. Particularly, the bioxazole derivative bearing piperazine groups was the most active compound of the investigated series, whereas the derivatives bearing morpholine groups were the most selective ones on cancer cells, in full agreement with their ability to act as the strongest and most selective G-quadruplex ligands, respectively.

Basic protein- and peptide-induced stabilization of long-loop DNA G-guadruplexes

The human genome contains many G-quadruplex-forming sequences, including sequences containing long single-stranded loops that are believed to be unfavorable for G-quadruplex formation. The intracellular environment of biological cells is crowded with proteins with charged surfaces. Understanding the effects of protein-rich environments is important for understanding the formation of G-quadruplexes in an intracellular environment. In this study, we investigated the structural stability of DNA G-quadruplexes in the presence of several types of globular proteins (lysozyme, cytochrome c, bovine serum albumin, myoglobin, histone proteins, and serum proteins), unstructured polypeptides (protamine and poly-l-lysine), and oligopeptides (RGG/RG-domain peptides and short repeated peptides). Thermal melting studies of G-quadruplex-forming oligonucleotides derived from the human telomeric repeat sequence revealed that environments containing high concentrations of proteins and peptides differently affected the G-quadruplex stability according to their loop lengths. We found that weak electrostatic interactions of G-quadruplex loops with basic proteins and peptides improved the stability of long-loop G-quadruplexes and the interactions were strengthened under crowded conditions simulated by dextran. The comparison of the effects of different types of proteins and peptides indicated that excluded volume interactions and structural flexibility of both DNA and polypeptide chains influenced the efficiency of their interactions. This study provides insights into long-loop G-quadruplex stability in a crowded intracellular environment and the recognition of G-quadruplexes by arginine-rich domains of G-quadruplex-binding proteins.

Recognition and coacervation of G-quadruplexes by a multifunctional disordered region in RECQ4 helicase

Biomolecular polyelectrolyte complexes can be formed between oppositely charged intrinsically disordered regions (IDRs) of proteins or between IDRs and nucleic acids. Highly charged IDRs are abundant in the nucleus, yet few have been functionally characterized. Here, we show that a positively charged IDR within the human ATP-dependent DNA helicase Q4 (RECQ4) forms coacervates with G-quadruplexes (G4s). We describe a three-step model of charge-driven coacervation by integrating equilibrium and kinetic binding data in a global numerical model. The oppositely charged IDR and G4 molecules form a complex in the solution that follows a rapid nucleation-growth mechanism leading to a dynamic equilibrium between dilute and condensed phases. We also discover a physical interaction with Replication Protein A (RPA) and demonstrate that the IDR can switch between the two extremes of the structural continuum of complexes. The structural, kinetic, and thermodynamic profile of its interactions revealed a dynamic disordered complex with nucleic acids and a static ordered complex with RPA protein. The two mutually exclusive binding modes suggest a regulatory role for the IDR in RECQ4 function by enabling molecular handoffs. Our study extends the functional repertoire of IDRs and demonstrates a role of polyelectrolyte complexes involved in G4 binding.

Parallel G-quadruplex recognition by neomycin.

G-quadruplex-forming nucleic acids have evolved to have applications in biology, drug design, sensing, and nanotechnology, to name a few. Together with the structural understanding, several attempts have been made to discover and design new classes of chemical agents that target these structures in the hope of using them as future therapeutics. Here, we report the binding of aminoglycosides, in particular neomycin, to parallel G-quadruplexes that exist as G-quadruplex monomers, dimers, or compounds that have the propensity to form dimeric G-quadruplex structures. Using a combination of calorimetric and spectroscopic studies, we show that neomycin binds to the parallel G-quadruplex with affinities in the range of Ka ∼ 105-108M-1, which depends on the base composition, ability to form dimeric G-quadruplex structures, salt, and pH of the buffer used. At pH 7.0, the binding of neomycin was found to be electrostatically driven potentially through the formation of ion pairs formed with the quadruplex. Lowering the pH resulted in neomycin's association constants in the range of Ka ∼ 106-107M-1 in a salt dependent manner. Circular dichroism (CD) studies showed that neomycin's binding does not cause a change in the parallel conformation of the G-quadruplex, yet some binding-induced changes in the intensity of the CD signals were seen. A comparative binding study of neomycin and paromomycin using d(UG4T) showed paromomycin binding to be much weaker than neomycin, highlighting the importance of ring I in the recognition process. In toto, our results expanded the binding landscape of aminoglycosides where parallel G-quadruplexes have been discovered as one of the high-affinity sites. These results may offer a new understanding of some of the undesirable functions of aminoglycosides and help in the design of aminoglycoside-based G-quadruplex binders of high affinity.

Peptides Selected by G4-mRNA Display-Seq Enable RNA G-Quadruplex Recognition and Gene Regulation.

G-quadruplexes (G4s) are noncanonical secondary structures that play critical roles in both chemistry and biology. Although several approaches have been developed for G4 targeting, such as chemicals and antibodies, there is currently no general and efficient platform for G4-specific peptides. In this study, we developed a new platform, G4-mRNA display-Seq, for selecting peptides that specifically recognize the G4 target of interest. By using an RNA G4 (rG4) found in human telomerase RNA (hTERC) as the target, we have identified a novel short peptide, namely, peptide 11 (pep11), which displays high affinity and selectivity to hTERC rG4. Furthermore, we designed tandem and cyclic versions of pep11 and found that both modified versions exhibit stronger binding affinity with preferential rG4 selectivity. Notably, we have demonstrated that these peptides can negatively regulate gene expression by targeting rG4. Our results provide a universal platform for the discovery of G4-targeting peptides and demonstrate the ability of these peptides to regulate G4-mediated gene functions.

ON-OFF Fluorescent Cyanine Dye Based on a Benzothiophenyl Rotor Enables Selective Illumination of G-Quadruplexes in Mitochondria.

Conventional cyanine dyes exist as "always-on" fluorescent probes leading to inevitable background signals which often limit their performance and scope of applications. To develop specific fluorescent probes with high sensitivity and robust OFF/ON switching for targeting G4s, we introduced aromatic heterocycles through conjugation with polymethine chains to construct a rotor-π system. Here, a universal strategy is presented to synthesize pentamethine cyanines with different aromatic heterocycle substituents on the meso-polymethine chain. In these probes, SN-Cy5-S is self-quenched in aqueous solution due to H-aggregation. The structure indicates that SN-Cy5-S with a flexible meso-benzothiophenyl rotor conjugated to the cyanine backbone matches adaptively with G-tetrad planes, enhancing π-π stacking and resulting in triggered fluorescence. This allows recognition of G-quadruplexes due to the synergy of disaggregation-induced emission (DIE) and inhibited twisted intramolecular charge-transfer effects. This combination leads to a robust lighting-up fluorescence response for c-myc G4 with superior fluorescence enhancement (98-fold), allowing for a low detection limit of 1.51 nM, which is much more sensitive than the previously reported DIE-based G4 probes (22-83.5 nM). In addition, the superior imaging properties and rapid internalization time (5 min) in mitochondria allow SN-Cy5-S to also have a high potential for mitochondrially targeting anti-cancer therapy.

ALS-linked TDP-43 mutations interfere with the recruitment of RNA recognition motifs to G-quadruplex RNA

TDP-43 is a major pathological protein in sporadic and familial amyotrophic lateral sclerosis (ALS) and mediates mRNA fate. TDP-43 dysfunction leads to causes progressive degeneration of motor neurons, the details of which remain elusive. Elucidation of the molecular mechanisms of RNA binding could enhance our understanding of this devastating disease. We observed the involvement of the glycine-rich (GR) region of TDP-43 in the initial recognition and binding of G-quadruplex (G4)-RNA in conjunction with its RNA recognition motifs (RRM). We performed a molecular dissection of these intramolecular RNA-binding modules in this study. We confirmed that the ALS-linked mutations in the GR region lead to alteration in the G4 structure. In contrast, amino acid substitutions in the GR region alter the protein structure but do not void the interaction with G4-RNA. Based on these observations, we concluded that the structural distortion of G4 caused by these mutations interferes with RRM recruitment and leads to TDP-43 dysfunction. This intramolecular organization between RRM and GR regions modulates the overall G4-binding properties.

Abstract 3842: Berberine recognition of the dGMP-bound PDGFR-β promoter G-quadruplex: Structural insight into specific drug targeting

Abstract PDGFR-β (Platelet-Derived Growth Factor Receptor beta) is a receptor tyrosine kinase whose overexpression drives the progression and metastasis of many cancers. It is an established anticancer target and PDGFR-β inhibition via kinase inhibitors has been actively sought-after. However, PDGFR-β kinase inhibitors often lack specificity. The PDGFR-β gene promoter forms DNA G-quadruplexes that are transcription silencer whose stabilization by small molecules represses PDGFR-β expression. Therefore, targeting PDGFR-β promoter G-quadruplexes for transcriptional silencing is a promising alternative strategy for cancer therapy. G-quadruplex is an exciting family of non-canonical DNA secondary structures. DNA G-quadruplex within the PDGFR-β gene promoter forms novel vacancy pockets (vG4) that can be filled-in by guanine metabolites such as dGMP and cGMP. This presents an attractive target for small molecule targeting. Herein, we present the binding of the natural product berberine with the unique PDGFR-β dGMP-vG4 binary complex to form a novel ternary complex, the first case observed in DNA G-quadruplexes. Using circular dichroism, fluorescence, and nuclear magnetic resonance (NMR) spectroscopy, we demonstrated that berberine binds with high affinity and strongly stabilizes the dGMP-fill-in PDGFR-β vG4. Our determined high-resolution NMR structure of this ternary complex in K+-containing solution reveals a 2:1 binding stoichiometry of berberine to the dGMP-fill-in PDGFR-β vG4. Significantly, one berberine directly stacks upon and extensively covers the dGMP. This direct binding mode provides structural basis for targeting the unique PDGFR-β promoter G-quadruplex by small molecules and suggests an intriguing strategy of designing drug-like, guanine-conjugated molecules to selectively silence the PDGFR-β gene. Because vG4 formation and dGMP fill-in is a unique property of the PDGFR-β promoter G-quadruplex, our study provides a structural basis for rationally designing small molecule drugs to specifically target the PDGFR-β promoter G-quadruplex to inhibit oncogenic PDGFR-β for cancer therapeutics. Citation Format: Kai-Bo Wang, Jonathan Dickerhoff, Yichen Han, Danzhou Yang. Berberine recognition of the dGMP-bound PDGFR-β promoter G-quadruplex: Structural insight into specific drug targeting. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3842.

DNA G-Quadruplex Recognition In Vitro and in Live Cells by a Structure-Specific Nanobody.

G-quadruplexes (G4s) are four-stranded DNA secondary structures that occur in the human genome and play key roles in transcription, replication, and genome stability. G4-specific molecular probes are of vital importance to elucidate the structure and function of G4s. The scFv antibody BG4 has been a widely used G4 probe but has various limitations, including relatively poor in vitro expression and the inability to be expressed intracellularly to interrogate G4s in live cells. To address these considerations, we describe herein the development of SG4, a camelid heavy-chain-only derived nanobody that was selected against the human Myc DNA G4 structure. SG4 exhibits low nanomolar affinity for a wide range of folded G4 structures in vitro. We employed AlphaFold combined with molecular dynamics simulations to construct a molecular model for the G4-nanobody interaction. The structural model accurately explains the role of key amino acids and Kd measurements of SG4 mutants, including arginine-to-alanine point mutations that dramatically diminish G4 binding affinity. Importantly, predicted amino acid-G4 interactions were subsequently confirmed experimentally by biophysical measurements. We demonstrate that the nanobody can be expressed intracellularly and used to image endogenous G4 structures in live cells. We also use the SG4 protein to positionally map G4s in situ and also on fixed chromatin. SG4 is a valuable, new tool for G4 detection and mapping in cells.

Alkali cation-mediated topology displayed by an exonic G-rich sequence of TRPA1 gene

G-rich sequences are intrinsic parts of the genome, widespread in promoters, telomeres, or other regulatory regions. The in vivo existence and biological significance have established the functional aspect of G-quadruplex structures and thus have developed immense interest in exploring their therapeutic aspects. Herein, using biophysical methods, we examined the structural status and comprehensive cation-dependence of a 17-bp G-rich genomic sequence (SKGT17) located in the coding region of the human TRPA1 gene, known to be associated with various neurovascular, cardiovascular, and respiratory conditions. TRPA1 is primarily seen as a therapeutic target for the development of novel analgesics. Bioinformatics analysis has suggested that 17-bp quadruplex motif is a binding site for transcription factor 'Sp1'. The formation and recognition of SKGT17 G-quadruplex might impact its regulatory functioning. Biophysical studies confirmed that the presence of alkali metal ions facilitated the formation of G-quadruplex in parallel topology. Native gel further substantiated the formation of a biomolecular species. Circular dichroism (CD), UV-thermal melting (Tm), and CD melting confirmed the formation of parallel G-quadruplex with metal ion-dependent stability. The stability of the G-quadruplex formed is found to be significantly high in the presence of K+ ions than that of other ions. Intriguingly, we have also established that this segment of the TRAP1 gene favors G-quadruplex formation over its participation in the corresponding duplex formation under K+ ions conditions. This study attempts to explain the rationale for the stabilization of G-quadruplex in the presence of alkali metal ions and may add to a better understanding and insights into DNA-metal ions interactions.

Thioflavine T-induced charge neutralization assembly of AuNPs for colorimetric sensing of thallium

Thallium (Tl) is regarded as one of the 129 so-called “priority pollutants”, but its rapid optical sensing is largely unexplored. In this work, an AuNP-based label-free colorimetric sensing scheme was developed for Tl + . Specifically, thioflavine T (ThT) was found to induce charge neutralization aggregation of AuNPs, resulting in stable and intense blue color of AuNPs. Due to the higher affinity of PS2. M (DNA)-AuNPs over PS2. M-ThT, PS2. M DNA would protect AuNPs from aggregation by ThT. Since the affinity of PS2. M DNA-Tl + was even higher than that of PS2. M DNA-AuNPs, in the presence of Tl + , PS2. M DNA would be first captured by Tl + and restricted to be adsorbed onto AuNPs, resulting in ThT-induced aggregation of AuNPs for colorimetric sensing of Tl + . The proposed colorimetric sensing offered a limit of detection (LOD, 3σ) of 3.2 nM, which was lower than the maximum permitted amount of Tl + in drinking water regulated by EPA (10 nM). The accuracy of the proposed method was first verified through analysis of six water samples. Furthermore, the proposed colorimetric system was also explored for real-time monitoring of Tl + leakage from coal mine during raining water soaking, and maximum Tl + amounts occurred at about 12–24 h. ThT-induced charge screening assembly of AuNPs was harvested for colorimetric detection of Tl + in combination with G-quadruplex recognition. • ThT, a G-quadruplex dye, was found to induce charge screening assembly of AuNPs. • A colorimetric approach was developed for facile Tl+ detection in environmental water samples. • The method was explore for real-time monitoring of Tl + leakage from coal mine during raining water soaking.

Visualization of ligand-induced c-MYC duplex-quadruplex transition and direct exploration of the altered c-MYC DNA-protein interactions in cells.

Ligand-Induced duplex-quadruplex transition within the c-MYC promoter region is one of the most studied and advanced ideas for c-MYC regulation. Despite its importance, there is a lack of methods for monitoring such process in cells, hindering a better understanding of the essence of c-MYC G-quadruplex as a drug target. Here we developed a new fluorescent probe ISCH-MYC for specific c-MYC G-quadruplex recognition based on GTFH (G-quadruplex-Triggered Fluorogenic Hybridization) strategy. We validated that ISCH-MYC displayed distinct fluorescence enhancement upon binding to c-MYC G-quadruplex, which allowed the duplex-quadruplex transition detection of c-MYC G-rich DNA in cells. Using ISCH-MYC, we successfully characterized the induction of duplex to G-quadruplex transition in the presence of G-quadruplex stabilizing ligand PDS and further monitored and evaluated the altered interactions of relevant transcription factors Sp1 and CNBP with c-MYC G-rich DNA. Thus, our study provides a visualization strategy to explore the mechanism of G-quadruplex stabilizing ligand action on c-MYC G-rich DNA and relevant proteins, thereby empowering future drug discovery efforts targeting G-quadruplexes.

A smart small molecule as specific fluorescent probe for sensitive recognition of mitochondrial DNA G-Quadruplexes

G-quadruplex (G4) has become an essential target for the therapy of human genetic diseases (cancer included) with important biological functions for regulation and monitoring. In contrast, little information about G-quadruplexes in mitochondria is known due to the limited development of fluorescent ligands for mitochondrial DNA (mtDNA) G4 detection, urging the design of fluorogenic detection ligands. Herein, we designed and synthesized a robust aggregation-induced emission ligand SPN for recognition of mtDNA G4s, which integrates a G4-active photosensitizer (BZT-triphenylamine) molecule and a mitochondrial targeting functional group (lipophilic triphenylphosphonium cation). Using SPN as the mtDNA G4s sensor, we surprisingly found that SPN could achieve sensitive recognition, sensing, and stabilization of the G4s with the detection limit as low as 0.89 nM. SPN can be highly colocalized with mitochondria, allowing monitoring of mtDNA G4s effectively in vitro. Remarkably, the fluorescence intensity in cancer cells is significantly stronger than that in normal cells, suggesting the potential applications of SPN in cancer diagnosis. This study provides a promising example of designing a fluorescent probe targeting and sensing mtDNA G4s and offers a feasible chemical tool for investigating mtDNA G4s.

Synthesis and characterization of fluorescence active G4-quartet and direct evaluation of self-assembly impact on emission

Fluorescence (FL) active 8-aryl guanosine derivatives were prepared and applied for cation mediated self-assembly to form the H-bonded G8-quadruplexes. The p-cyano (p-CN) and 8-anthracene (8-An) substituted guanosines were identified to give the strongest fluorescence with the formation of G8-octamers (G8) both in solution (NMR) and solid state (X-ray). This well-defined G8-octamer system has provided the first direct evidence on the self-assembled G-quadruplex fluorescence emission with aggregation-induced emission (AIE), which could be applied as the foundation for FL molecular probe design toward G-quadruplex recognition.

A Smart Small Molecule as Specific Fluorescent Probe for Ultrasensitive Recognition of Mitochondrial G-Quadruplexes

A Smart Small Molecule as Specific Fluorescent Probe for Ultrasensitive Recognition of Mitochondrial G-Quadruplexes