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Search Results (428)

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Keywords = G-quadruplex DNA

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22 pages, 9633 KiB  
Article
Mouse PrimPol Outperforms Its Human Counterpart as a Robust DNA Primase
by Gustavo Carvalho, Susana Guerra, María I. Martínez-Jiménez and Luis Blanco
Int. J. Mol. Sci. 2025, 26(14), 6947; https://doi.org/10.3390/ijms26146947 - 19 Jul 2025
Viewed by 260
Abstract
The human PrimPol counteracts DNA replication stress by repriming DNA synthesis when fork progression is hindered by UV light or hydroxyurea treatment, or by encountering complex DNA structures, such as G-quadruplexes, R-loops, or interstrand crosslinks. The Mus musculus PrimPol (MmPrimPol) shares [...] Read more.
The human PrimPol counteracts DNA replication stress by repriming DNA synthesis when fork progression is hindered by UV light or hydroxyurea treatment, or by encountering complex DNA structures, such as G-quadruplexes, R-loops, or interstrand crosslinks. The Mus musculus PrimPol (MmPrimPol) shares a high degree of amino acid similarity with its human ortholog; however, as shown here, MmPrimPol exhibits a more powerful primase activity compared to the human enzyme. Such a robust primase activity relies on an enhanced ability to bind the 5′ site nucleotide, and consequently to form initial dimers and further mature primers. Additionally, a shorter linker between the AEP core and the Zn finger domain (ZnFD) in the murine homolog likely promotes a constitutive closing of these domains into a primase-ready configuration. Consequently, a reinforced close configuration of the ZnFD would explain why MmPrimPol has a more robust primase, but a very limited DNA polymerization on an existing primer. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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21 pages, 2524 KiB  
Article
The Relevance of G-Quadruplexes in Gene Promoters and the First Introns Associated with Transcriptional Regulation in Breast Cancer
by Huiling Shu, Ke Xiao, Wenyong Zhu, Rongxin Zhang, Tiantong Tao and Xiao Sun
Int. J. Mol. Sci. 2025, 26(14), 6874; https://doi.org/10.3390/ijms26146874 - 17 Jul 2025
Viewed by 221
Abstract
The role of G-quadruplexes (G4s) in gene regulation has been widely documented, especially in gene promoters. However, the transcriptional mechanisms involving G4s in other regulatory regions remain largely unexplored. In this study, we integrated the G4-DNA data derived from 22 breast cancer patient-derived [...] Read more.
The role of G-quadruplexes (G4s) in gene regulation has been widely documented, especially in gene promoters. However, the transcriptional mechanisms involving G4s in other regulatory regions remain largely unexplored. In this study, we integrated the G4-DNA data derived from 22 breast cancer patient-derived tumor xenograft (PDTX) models and MCF7 cell line as potential breast cancer-associated G4s (BC-G4s). Genome-wide analysis showed that BC-G4s are more prevalent in gene promoters and the first introns. The genes accommodating promoter or intronic BC-G4s show significantly higher transcriptional output than their non-G4 counterparts. The biased distribution of BC-G4s in close proximity to the transcription start site (TSS) is associated with an enrichment of transcription factor (TF) interactions. A significant negative correlation was detected between the G4–TF interactions within the first introns and their cognate promoters. These different interactions are complementary rather than redundant. Furthermore, the differentially expressed genes (DEGs) harboring promoter and first intron BC-G4s are significantly enriched in the cell cycle pathway. Notably, promoter BC-G4s of DEGs could be a central hub for TF–TF co-occurrence. Our analysis also revealed that G4-related single nucleotide variants (SNVs) affect the stability of G4 structures and the transcription of disease-related genes. Collectively, our results shed light on how BC-G4s within promoters and first introns regulate gene expression and reinforce the critical role of G4s and G4-related genes in breast cancer-associated processes. Full article
(This article belongs to the Special Issue Molecular Research of Multi-omics in Cancer)
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49 pages, 5285 KiB  
Review
Insights into Natural Products from Marine-Derived Fungi with Antimycobacterial Properties: Opportunities and Challenges
by Muhammad Azhari, Novi Merliani, Marlia Singgih, Masayoshi Arai and Elin Julianti
Mar. Drugs 2025, 23(7), 279; https://doi.org/10.3390/md23070279 - 3 Jul 2025
Viewed by 665
Abstract
Tuberculosis (TB) poses a persistent global health threat exacerbated by the emergence of drug-resistant strains; hence, there is a continuous quest for novel antimicrobial agents. Despite efforts to develop effective therapies, existing treatments require a relatively long duration of therapy to eradicate the [...] Read more.
Tuberculosis (TB) poses a persistent global health threat exacerbated by the emergence of drug-resistant strains; hence, there is a continuous quest for novel antimicrobial agents. Despite efforts to develop effective therapies, existing treatments require a relatively long duration of therapy to eradicate the pathogen due to its virulence factors, pathogenesis patterns, and ability to enter dormant states. This can lead to a higher risk of treatment failure due to poor patient adherence to the complex regimen. As a result, considerable research is necessary to identify alternative antituberculosis agents. The marine environment, particularly marine-derived fungi, has recently gained interest due to its potential as an abundant source of bioactive natural products. This review covers 19 genera of marine-derived fungi and 139 metabolites, 131 of which exhibit antimycobacterial activity. The integrated dataset pinpoints the fungal genera and chemical classes that most frequently yield potent antimycobacterial hits while simultaneously exposing critical gaps, such as the minimal evaluation of compounds against dormant bacilli and the presence of underexplored ecological niches and fungal genera. Several compounds exhibit potent activity through uncommon mechanisms, including the inhibition of mycobacterial protein tyrosine phosphatases (MptpB/MptpA), protein kinase PknG, ATP synthase and the disruption of mycobacterial DNA via G-quadruplex stabilization. Structure–activity relationship (SAR) trends are highlighted for the most potent agents, illuminating how specific functional groups underpin target engagement and potency. This review also briefly proposes a dereplication strategy and approaches for toxicity mitigation in the exploration of marine-derived fungi’s natural products. Through this analysis, we offer insights into the potency and challenges of marine-derived fungi’s natural products as hit compounds or scaffolds for further antimycobacterial research. Full article
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30 pages, 29722 KiB  
Article
Modeling Possible G-Quadruplexes and i-Motifs at DNA–DNA Contact Sites: Strategy, Classification, and Examples
by Vladimir B. Tsvetkov
Int. J. Mol. Sci. 2025, 26(13), 5979; https://doi.org/10.3390/ijms26135979 - 21 Jun 2025
Viewed by 431
Abstract
Tetrahelical DNA structures, such as G-quadruplexes (G4s) or i-motifs (iMs), are adopted by sequences comprising several G/C tracts, exist in equilibria with respective duplexes, and may contribute to genomic instability upon helicase deficiency. To understand genomic rearrangements resulting from the juxtaposition of G/C-rich [...] Read more.
Tetrahelical DNA structures, such as G-quadruplexes (G4s) or i-motifs (iMs), are adopted by sequences comprising several G/C tracts, exist in equilibria with respective duplexes, and may contribute to genomic instability upon helicase deficiency. To understand genomic rearrangements resulting from the juxtaposition of G/C-rich DNA duplexes, models of possible intermediate structures are needed. In this study, a general strategy for creating and verifying in silico 3D models of tetrahelical DNA was proposed. This strategy was used to investigate contacts of two or more duplexes with n G3/C3 tracts (n = 2–6) separated by T/A nucleotides. The revealed viable structures of DNA–DNA contacts include stacks of right-handed and left-handed G-quadruplexes (G4s), Holliday structure-resembling assemblies with the G4 and iM opposite each other on the borders of the central “hole”, etc. Based on molecular dynamic simulations, the most probable variants were determined by estimating the contributions to the free energy. The results may be used to clarify the mechanisms of strand exchange and other rearrangements upon DNA breaks near prolonged G/C-rich sites in living systems. Additionally, they provide a balanced view on the polymorphic versus programmed DNA assemblies in artificial systems. Full article
(This article belongs to the Collection State-of-the-Art Macromolecules in Russia)
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19 pages, 6213 KiB  
Article
Studies upon Fluorescent Modulation of Silver Nanoclusters Formed on Bifunctional DNA Template
by Patrycja Filipczuk, Agnieszka Fedoruk-Wyszomirska, Joanna Nowak-Karnowska, Zuzanna Pietralik-Molińska, Ewa Banachowicz, Maciej Kozak and Anna Dembska
Int. J. Mol. Sci. 2025, 26(10), 4914; https://doi.org/10.3390/ijms26104914 - 20 May 2025
Viewed by 525
Abstract
The use of DNA as a scaffold for nanoclusters is particularly interesting due to its structural versatility and easy integration with aptamers. In their structure, aptamers often contain non-canonical forms of DNA, i.e., G-quadruplexes (GQs). Four-stranded GQs are used to construct nanomachines and [...] Read more.
The use of DNA as a scaffold for nanoclusters is particularly interesting due to its structural versatility and easy integration with aptamers. In their structure, aptamers often contain non-canonical forms of DNA, i.e., G-quadruplexes (GQs). Four-stranded GQs are used to construct nanomachines and biosensors for monitoring changes in the concentration of potassium ions. In the present study, we continue our work related to the synthesis of silver nanoclusters formed on a bifunctional DNA template. By attaching a cytosine-rich domain (C12) to a G-quadruplex-forming sequence—human telomeric (Tel22) or thrombin-binding aptamer (TBA)—we constructed bifunctional templates for fluorescent silver nanoclusters (C12) with the ability to detect potassium ions (GQs). The changing localization of the C12 domain from the 3′ to 5′ end of the oligonucleotide was a successful way to improve the fluorescence properties of the obtained fluorescent probes. The best performance as a probe for potassium ions was exhibited by C12Tel22-AgNCs, with an LOD of 0.68 mM in PBS. The introduction of the fluorescent cytosine analog tC leads to an LOD of 0.68 mM in PBS and 0.46 mM in Tris-acetate. Additionally, we performed AFM, TEM, DLS analysis, and cellular studies to further investigate the structural properties and behavior of the Tel22C12-AgNCs in biological contexts. Full article
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13 pages, 1200 KiB  
Article
Using UV–Vis Titration to Elucidate Novel Epigallocatechin Gallate (EGCG)-Induced Binding of the c-MYC G-Quadruplex
by Justin Tang
Pharmaceuticals 2025, 18(5), 719; https://doi.org/10.3390/ph18050719 - 14 May 2025
Cited by 1 | Viewed by 603
Abstract
Background/Objectives: Aberrant expression of c-MYC drives aggressive cancers. A guanine-rich promoter sequence (Pu27) folds into a transcriptionally repressive G-quadruplex (G4). Epigallocatechin gallate (EGCG), the main green tea polyphenol, displays anticancer activity, but clear, easily replicated evidence for direct binding to the c-MYC G4 [...] Read more.
Background/Objectives: Aberrant expression of c-MYC drives aggressive cancers. A guanine-rich promoter sequence (Pu27) folds into a transcriptionally repressive G-quadruplex (G4). Epigallocatechin gallate (EGCG), the main green tea polyphenol, displays anticancer activity, but clear, easily replicated evidence for direct binding to the c-MYC G4 is lacking. We therefore obtained the first biophysical confirmation of an EGCG–c-MYC G4 interaction using routine UV–visible spectroscopy. Methods: A pre-annealed Pu27 G4 (5 µM) in potassium-rich buffer was titrated with freshly prepared EGCG (0–20 µM) at 25 °C. Full-range UV–Vis spectra (220–400 nm) were recorded after each addition, and absorbance variations at the DNA (260 nm) and ligand (275 nm) maxima were quantified across three independent replicates. Results: EGCG induced pronounced, concentration-dependent hyperchromicity at 260 nm, reaching ~8–10% above baseline at a 4:1 ligand/DNA ratio and exhibiting saturable binding behaviour. Concurrently, the 275 nm band displayed relative hypochromicity coupled with a subtle bathochromic shift. These reciprocal perturbations—absent in buffer-only controls—constitute definitive evidence of a specific EGCG•G4 complex most consistent with external π-stacking or groove engagement rather than intercalation. Conclusions: This study delivers the first rigorous, quantitative UV–Vis confirmation that a readily consumed dietary polyphenol directly targets the c-MYC promoter G4. By marrying conceptual elegance with methodological accessibility, it provides a compelling molecular rationale for EGCG’s anti-oncogenic repertoire, inaugurates an expedient platform for screening G4-reactive nutraceuticals, and paves the way for structural and cellular investigations en route to next-generation c-MYC-directed therapies. Full article
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15 pages, 2573 KiB  
Article
The DNA Topoisomerase 1 Contributes to Stress Response in Saccharomyces cerevisiae, Regardless Its Catalytic Activity
by Anna D’Alfonso, Alessandra Egidi, Ludovica Proietti and Giorgio Camilloni
Biology 2025, 14(5), 499; https://doi.org/10.3390/biology14050499 - 3 May 2025
Viewed by 388
Abstract
In this study, we examined the activation of the ATG8, HSP12, KGD1, and POT1 genes in response to decreased glucose levels in the culture medium. Our results show that in top1Δ strains, gene activation is further enhanced compared to WT strains under low [...] Read more.
In this study, we examined the activation of the ATG8, HSP12, KGD1, and POT1 genes in response to decreased glucose levels in the culture medium. Our results show that in top1Δ strains, gene activation is further enhanced compared to WT strains under low glucose conditions, indicating that Top1p represses these genes. This repression occurs independently of its catalytic function. We investigated Rpd3p as an interacting factor of Top1p and found that in rpd3Δ mutants, gene expression under low glucose conditions is even higher than in top1Δ strains, suggesting that Rpd3p also acts as a negative regulator. ChIP analysis revealed that while Top1p levels in regulatory regions remain constant, Rpd3 recruitment increases on promoters after glucose reduction in WT strains but significantly decreases in top1Δ strains. Overall, our findings suggest that Rpd3p is recruited by Top1p to regulate gene expression at controlled physiological levels, highlighting the role of Top1p in transcriptional regulation, controlling helical stress, and interacting with key regulatory factors in response to environmental changes. Full article
(This article belongs to the Section Biochemistry and Molecular Biology)
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15 pages, 539 KiB  
Review
G-Quadruplexes in Tumor Immune Regulation: Molecular Mechanisms and Therapeutic Prospects in Gastrointestinal Cancers
by Yunxia Zhou, Difei Xu, Ying Zhang and Huaixiang Zhou
Biomedicines 2025, 13(5), 1057; https://doi.org/10.3390/biomedicines13051057 - 27 Apr 2025
Viewed by 832
Abstract
G-quadruplex (G4) is a noncanonical nucleic acid secondary structure self-assembled by guanine-rich sequences. Recent studies have not only revealed the key role of G4 in gene regulation, DNA replication, and telomere maintenance but also showed that it plays a core role in regulating [...] Read more.
G-quadruplex (G4) is a noncanonical nucleic acid secondary structure self-assembled by guanine-rich sequences. Recent studies have not only revealed the key role of G4 in gene regulation, DNA replication, and telomere maintenance but also showed that it plays a core role in regulating the tumor immune microenvironment. G4 participates in tumor immune escape and the inhibition of immune response by regulating immune checkpoint molecules, cytokine expression, immune cell function, and their interaction network, thus significantly affecting the effect of tumor immunotherapy. This article systematically reviews the molecular mechanism of G4 in tumor immune regulation, especially gastrointestinal tumors, and explores the potential and application prospects of G4-targeted drug strategies in improving anti-tumor immunotherapy. Full article
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29 pages, 30337 KiB  
Review
Triplexes Color the Chromaverse by Modulating Nucleosome Phasing and Anchoring Chromatin Condensates
by Alan Herbert
Int. J. Mol. Sci. 2025, 26(9), 4032; https://doi.org/10.3390/ijms26094032 - 24 Apr 2025
Viewed by 945
Abstract
Genomic sequences that form three-stranded triplexes (TPXs) under physiological conditions (called T-flipons) play an important role in defining DNA nucleosome-free regions (NFRs). Within these NFRs, other flipon types can cycle conformations to actuate gene expression. The transcripts read from the NFR form condensates [...] Read more.
Genomic sequences that form three-stranded triplexes (TPXs) under physiological conditions (called T-flipons) play an important role in defining DNA nucleosome-free regions (NFRs). Within these NFRs, other flipon types can cycle conformations to actuate gene expression. The transcripts read from the NFR form condensates that engage proteins and small RNAs. The helicases bound then trigger RNA polymerase release by dissociating the 7SK ribonucleoprotein. The TPXs formed usually incorporate RNA as the third strand. TPXs made only from DNA arise mostly during DNA replication. Many small RNA types (sRNAs) and long noncoding (lncRNA) can direct TPX formation. TPXs made with circular RNAs have greater stability and specificity than those formed with linear RNAs. LncRNAs can affect local gene expression through TPX formation and transcriptional interference. The condensates seeded by lncRNAs are updated by feedback loops involving proteins and noncoding RNAs from the genes they regulate. Some lncRNAs also target distant loci in a sequence-specific manner. Overall, lncRNAs can rapidly evolve by adding or subtracting sequence motifs that modify the condensates they nucleate. LncRNAs show less sequence conservation than protein-coding sequences. TPXs formed by lncRNAs and sRNAs help place nucleosomes to restrict endogenous retroelement (ERE) expression. The silencing of EREs starts early in embryogenesis and is essential for bootstrapping development. Once the system is set, EREs play a different role, with a notable enrichment of Short Interspersed Nuclear Repeats (SINEs) in Enhancer–Promoter condensates. The highly programmable TPX-dependent processes create a chromaverse capable of many complexities. Full article
(This article belongs to the Collection Feature Papers in Molecular Genetics and Genomics)
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23 pages, 2234 KiB  
Review
Recent Progress and Potential of G4 Ligands in Cancer Immunotherapy
by Jiahui Lin, Zhu Gong, Yingyue Lu, Jiongheng Cai, Junjie Zhang, Jiaheng Tan, Zhishu Huang and Shuobin Chen
Molecules 2025, 30(8), 1805; https://doi.org/10.3390/molecules30081805 - 17 Apr 2025
Viewed by 1369
Abstract
G-quadruplex (G4) structures are non-canonical nucleic acid conformations that play crucial roles in gene regulation, DNA replication, and telomere maintenance. Recent studies have highlighted G4 ligands as promising anticancer agents due to their ability to modulate oncogene expression and induce DNA damage. By [...] Read more.
G-quadruplex (G4) structures are non-canonical nucleic acid conformations that play crucial roles in gene regulation, DNA replication, and telomere maintenance. Recent studies have highlighted G4 ligands as promising anticancer agents due to their ability to modulate oncogene expression and induce DNA damage. By stabilizing G4 structures, these ligands affect tumor progression. Additionally, they have been implicated in tumor immunity modulation, particularly through the activation and immunogenic cell death induction of the cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway. Moreover, their disruption of telomere maintenance and regulation of key oncogenes, such as c-MYC and KRAS, position them as candidates for immune-based therapeutic interventions. Despite their therapeutic potential, challenges remain in optimizing their clinical applications, particularly in patient stratification and elucidating their immunomodulatory effects. This review provides a comprehensive overview of the mechanisms through which G4 ligands influence tumor progression and immune regulation, highlighting their potential role in future cancer immunotherapy strategies. Full article
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19 pages, 13029 KiB  
Article
Decoding G-Quadruplexes Sequence in Vitis vinifera: Regulatory Region Enrichment, Drought Stress Adaptation, and Sugar–Acid Metabolism Modulation
by Jun Xie, Kangkang Song, Gaixia Qiao, Rong Wang, Hongyuan Wu, Qiaoxia Jia, Yujuan Liu, Yi Li and Meilong Xu
Plants 2025, 14(8), 1180; https://doi.org/10.3390/plants14081180 - 10 Apr 2025
Viewed by 653
Abstract
G-quadruplexes play a crucial role in transcription, translation, and DNA replication in plant genomes. Here, we comprehensively examined the prevalence and functions of G-quadruplexes in Vitis vinifera. A total of 467,813 G-quadruplexes were identified in grapevine genome, with enrichment in the promoter [...] Read more.
G-quadruplexes play a crucial role in transcription, translation, and DNA replication in plant genomes. Here, we comprehensively examined the prevalence and functions of G-quadruplexes in Vitis vinifera. A total of 467,813 G-quadruplexes were identified in grapevine genome, with enrichment in the promoter (0.54/kbp) and near transcription start sites (TSSs, 1.00/kbp), and showed conservative strand preference. The G-quadruplex density in centromeres exhibited heterogeneity. The differentially expressed genes (DEGs) under two-day drought stress manifested high G-quadruplex density in the promoter and TSS regions. The upregulated DEGs showed template strand-biased G-quadruplex enrichment, while downregulated DEGs displayed coding strand dominance linked to metal ion homeostasis and sugar–acid metabolism pathways, respectively. G-quadruplexes were enriched in key sugar–acid metabolism genes, including pyruvate kinase and sucrose synthase. The number of G-quadruplexes in sucrose transferase VINV genes was higher than that in the CWINV and NINV genes. This study revealed G-quadruplexes as regulatory elements of stress response and berry development, providing abundant genetic targets for precision breeding and the quality improvement of grapevines. Full article
(This article belongs to the Special Issue Bioinformatics and Functional Genomics in Modern Plant Science)
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21 pages, 4223 KiB  
Article
Exploring the G-Quadruplex Formation of AS1411 Derivatives
by Pedro Lourenço, David Moreira, André Miranda, Jéssica Lopes-Nunes, Izamara Maocha, Tiago Santos, Pedro L. Ferreira, Fani Sousa, Artur Paiva and Carla Cruz
Molecules 2025, 30(8), 1673; https://doi.org/10.3390/molecules30081673 - 8 Apr 2025
Viewed by 1046
Abstract
AS1411 is a G-quadruplex (G4) aptamer that binds tightly to nucleolin (NCL) on the cell surface and has shown strong anticancer effects. However, this aptamer is highly polymorphic, presenting different types of G4s, which may hinder its preclinical application. Several modifications have been [...] Read more.
AS1411 is a G-quadruplex (G4) aptamer that binds tightly to nucleolin (NCL) on the cell surface and has shown strong anticancer effects. However, this aptamer is highly polymorphic, presenting different types of G4s, which may hinder its preclinical application. Several modifications have been made to decrease the polymorphism of this aptamer. In this work, we designed six AS1411 derivatives by substituting guanine with thymine in the central linker and modifying the number of thymines either in the linker itself and/or at both ends of the sequence. The G4 formation, stability, and NCL binding were evaluated by several biophysical techniques and computational and cell studies. Overall, a decrease in polymorphism of G4-forming sequences compared to AS1411 is observed by size exclusion chromatography (SEC) and circular dichroism (CD) spectroscopy in the presence of potassium salt. The melting experiments reveal a higher ability of the derivatives without thymine at both sequence ends to form a G4, consistent with the G4H score predictions. Additionally, it is possible to conclude that deletions of T in the central core increase the ability to form G4. Moreover, the AS1411 derivatives bind NCL with high affinity (KD values in the 10−9 M range), particularly the sequences with only thymine modifications in the central linker. In silico studies reveal structural insights and demonstrate that AS1411 derivatives interact with NCL, establishing multiple interactions with the different domains, thereby further supporting the experimental findings. By using a lung cancer cell line with high cell surface NCL expression, we evaluate the internalization and uptake of AS1411 derivatives, identifying the derivative-lacking thymines in the central core as the ones with the highest internalization and cellular uptake. Full article
(This article belongs to the Special Issue Chemistry of Nucleic Acids: From Structure to Biological Interactions)
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12 pages, 4942 KiB  
Article
Intermolecular Structure Conversion-Based G4-TDF Nanostructures Functionalized μPADs for Fluorescent Determination of Potassium Ion in Serum
by Mengqi Wang, Xiuli Fu, Yixuan Liu, Zhiyang Zhang, Chenyu Jiang and Dean Song
Biosensors 2025, 15(4), 223; https://doi.org/10.3390/bios15040223 - 31 Mar 2025
Viewed by 422
Abstract
Herein, we proposed a versatile G-quadruplex (G4)-tetrahedral DNA framework (G4-TDF) nanostructure functionalized origami microfluidic paper-based device (μPADs) for fluorescence detection of K+ by lighting up thioflavin T (ThT). In this work, TDF provided robust structural support for G-rich sequence in well-defined orientation [...] Read more.
Herein, we proposed a versatile G-quadruplex (G4)-tetrahedral DNA framework (G4-TDF) nanostructure functionalized origami microfluidic paper-based device (μPADs) for fluorescence detection of K+ by lighting up thioflavin T (ThT). In this work, TDF provided robust structural support for G-rich sequence in well-defined orientation and spacing to ensure high recognition efficiency, enabling sensitive fluorescence sensing on origami μPAD. After introducing ThT, the G-rich sequences extended from TDF vertices formed a parallel G4 structure, showing weak fluorescence signal output. Upon the presence of target K+, this parallel G4 structure transitioned to antiparallel G4 structure, leading to a significantly increase in fluorescence signal of ThT. Benefiting from the outstanding fluorescence enhancement characteristic of the G4 structure for ThT and excellent specificity of the G4 structure to K+ plus satisfactory recognition efficiency with the aid of TDF, this origami paper-based fluorescence sensing strategy exhibited an impressive detection limit as low as 0.2 mM with a wide range of 0.5–5.5 mM. This innovative G4-TDF fluorescence sensing was applied for the first time on μPAD, providing a simple, effective, and rapid method for K+ detection in human serum with significant potential for clinical diagnostics. Full article
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61 pages, 23396 KiB  
Review
Porphyrins as Chiroptical Conformational Probes for Biomolecules
by Gabriele Travagliante, Massimiliano Gaeta, Roberto Purrello and Alessandro D’Urso
Molecules 2025, 30(7), 1512; https://doi.org/10.3390/molecules30071512 - 28 Mar 2025
Viewed by 717
Abstract
Porphyrins are highly conjugated macrocyclic compounds that possess exceptional photophysical and chemical properties, progressively establishing themselves as versatile tools in the structural investigation of biomolecules. This review explores their role as chiroptical conformational probes, focusing on their interactions with DNA and RNA. The [...] Read more.
Porphyrins are highly conjugated macrocyclic compounds that possess exceptional photophysical and chemical properties, progressively establishing themselves as versatile tools in the structural investigation of biomolecules. This review explores their role as chiroptical conformational probes, focusing on their interactions with DNA and RNA. The planar electron rich structure of porphyrin macrocycle that promote π–π interactions, their easy functionalization at the meso positions, and their capacity to coordinate metal ions enable their use in probing nucleic acid structures with high sensitivity. Emphasis is placed on their induced circular dichroism (ICD) signals in the Soret region, which provide precise diagnostic insights into binding mechanisms and molecular interactions. The review examines the interactions of porphyrins with various DNA structures, including B-, Z-, and A-DNA, single-stranded DNA, and G-quadruplex DNA, as well as less common structures like I-motif and E-motif DNA. The last part highlights recent advancements in the use of porphyrins to probe RNA structures, emphasizing binding behaviors and chiroptical signals observed with RNA G-quadruplexes, as well as the challenges in interpreting ICD signals with other RNA motifs due to their inherent structural complexity. Full article
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26 pages, 14775 KiB  
Article
Conformational Propensities of a DNA Hairpin with a Stem Sequence from the c-MYC Promoter
by Arees Garabet, Iztok Prislan, Nataša Poklar Ulrih, James W. Wells and Tigran V. Chalikian
Biomolecules 2025, 15(4), 483; https://doi.org/10.3390/biom15040483 - 26 Mar 2025
Viewed by 566
Abstract
G-quadruplexes and i-motifs are four-stranded non-canonical structures of DNA. They exist in the cell, where they are implicated in the conformational regulation of cellular events, such as transcription, translation, DNA replication, telomere homeostasis, and genomic instability. Formation of the G-quadruplex and i [...] Read more.
G-quadruplexes and i-motifs are four-stranded non-canonical structures of DNA. They exist in the cell, where they are implicated in the conformational regulation of cellular events, such as transcription, translation, DNA replication, telomere homeostasis, and genomic instability. Formation of the G-quadruplex and i-motif conformations in the genome is controlled by their competition with the pre-existing duplex. The fate of that competition depends upon the relative stabilities of the competing conformations, leading ultimately to a distribution of double helical, tetrahelical, and coiled conformations that coexist in dynamic equilibrium with each other. We previously developed a CD spectroscopy-based procedure to characterize the distribution of conformations adopted by equimolar mixtures of complementary G- and C-rich DNA strands from the promoter regions of the c-MYC, VEGF, and Bcl-2 oncogenes. In those bimolecular systems, duplex-to-tetraplex and duplex-to-coil transitions are accompanied by strand separation and an associated entropic cost. This situation is distinct from the pseudo-monomolecular nature of conformational transformations within the genome, where strand separation does not occur. To mimic better the situation in the genome, we here extend our studies to a monomolecular DNA construct—a hairpin—in which complementary G- and C-rich strands featuring sequences from the promoter region of the c-MYC oncogene are linked by a dT11 loop. We used our CD-based procedure to quantify the distribution of conformational states sampled by the hairpin at pH 5.0 and 7.0 as a function of temperature and the concentration of KCl. The data were analyzed according to a thermodynamic model based on equilibria between the different conformational states to evaluate the thermodynamic properties of the duplex-to-coil, G-quadruplex-to-coil, and i-motif-to-coil transitions of the hairpin. The results have implications for the modulation of such transitions as a means of therapeutic intervention. Full article
(This article belongs to the Special Issue Insights from the Editorial Board Members)
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