Article
Chemistry, Multidisciplinary
Anirban Ghosh, Marko Trajkovski, Marie-Paule Teulade-Fichou, Valerie Gabelica, Janez Plavec
Summary: Human telomeric G-quadruplex DNA structures are attractive targets for anticancer drugs. However, the polymorphism of the target complicates drug design. This study reports the discovery of a G-quadruplex ligand that can completely change the fold of the DNA structure, providing valuable insights into the coordination structure of G-quadruplexes.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Aparna Bansal, Priyanka Phogat, Shrikant Kukreti
Summary: This study reveals the formation of an intramolecular non-conventional triplex structure by Chlamydomonas reinhardtii telomere in Na+ solution, which is stabilized by the co-existence of reverse Hoogsteen and Wobble base pairing.
Article
Biochemistry & Molecular Biology
Julien Marquevielle, Aurore De Rache, Brune Vialet, Estelle Morvan, Jean-Louis Mergny, Samir Amrane
Summary: The Caenorhabditis elegans model has provided insights into the role of G-quadruplexes in genomic instability. Telomeric sequences in C. elegans show similarities to those in humans, but even small changes in these sequences can have significant effects on the folded G-quadruplex structure. This study determined the structure of the C. elegans telomeric sequence, revealing an intramolecular two G-tetrads basket type G-quadruplex structure with a C-T base pair in the diagonal loop. The findings shed light on the telomeric structure of the widely used C. elegans animal model.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Chemistry, Medicinal
Domen Oblak, Hadzi, Crtomir Podlipnik, Jurij Lah
Summary: The authors investigated the (un)folding and binding process of a human telomeric fragment with ligands through calorimetry and spectroscopy. The results showed that the presence of specific ligands can alter the topology of G-quadruplex nucleic acids. By analyzing thermodynamic parameters and conducting molecular modeling, the driving forces behind the topological transformations were clarified.
Article
Biochemistry & Molecular Biology
Xiao-Dong Wang, Jia-Xin Wang, Ming-Hao Hu
Summary: In this study, a series of novel phenanthrene imidazoles targeting telomeric G4 were designed and synthesized, among which PI-2 was identified as the most promising ligand with high cytotoxicity, cellular uptake efficiency, and G4-interacting ability. Cellular studies showed that PI-2 inhibited the proliferation and migration of human and mouse triple-negative breast cancer cells and induced DNA damage response and immunogenic cell death. In vivo experiments demonstrated that PI-2-treated dying cells could effectively reduce tumor burden and promote the infiltration of CD8+ and CD4+ T cells in the tumor microenvironment, providing new insights for the development of G4-based immunochemotherapeutic agents.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Taniya Sharma, Nikita Kundu, Sarvpreet Kaur, Vibha Tandon, J. Shankaraswamy, Sarika Saxena
Summary: This study provides evidence of human telomeric G4 destabilization upon peptide binding in dilute and cell-mimicking conditions, suggesting the potential therapeutic targets for diseases with over-representation of G4 motifs.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Valentina Pirota, Chiara Platella, Domenica Musumeci, Alessandra Benassi, Jussara Amato, Bruno Pagano, Giorgio Colombo, Mauro Freccero, Filippo Doria, Daniela Montesarchio
Summary: NDI-5 has shown promising potential as a ligand for multimeric G4 structures, selectively targeting them over duplex DNA. Experimental analyses including CD, gel electrophoresis, ITC, and fluorescence spectroscopy suggest that NDI-5 effectively binds and stabilizes tel46 G4, favoring a hybrid folding in K+-containing buffer.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Nikita Kundu, Taniya Sharma, Sarvpreet Kaur, Aman Kumar Mahto, Rikeshwer Prasad Dewangan, J. Shankaraswamy, Sarika Saxena
Summary: This study provides the first evidence of human telomeric G4 destabilization upon peptide binding, which will open new research avenues for treating DNA-related diseases.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Di Bai, Song-Wang Shan, Xin Zhang, Yan Li, Jie Xie, Wen-Qiang Wu
Summary: In this study, the folding, dynamics induced by environment, and protein-catalyzed unfolding of plant telomeric G4s were comprehensively studied. It was found that various plant telomeric sequences can fold into G4 structures, and the stability of G4s in dilute solution is decreased by both 5' and 3' ssDNA. Molecular crowding promotes the formation of parallel structures for three-layer G4s and increases the stability of all selected G4s. AtRecQ2 helicase can resolve the stable parallel structure of typical plant telomeric G4 in crowded solution, while ssDNA binding protein AtRPA cannot. Furthermore, AtRecQ2 unwinds the structure more efficiently in the presence of AtRPA. These results expand our understanding of the structures and dynamics of plant telomeric G4s.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Luca Bertini, Valeria Libera, Francesca Ripanti, Francesca Natali, Marco Paolantoni, Andrea Orecchini, Alessandro Nucara, Caterina Petrillo, Lucia Comez, Alessandro Paciaroni
Summary: Telomeric G-quadruplexes (G4s) exhibit structural polymorphism and the dynamics of G4s are affected by conformation and complexation. In this study, the dynamics of Tel22 in different conformations and complexed with BRACO19 ligand were investigated. The results showed that hydration water played a role in mediating the effect of polymorphism and complexation on the fast dynamics of G4s.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Benedetta Petra Rosi, Valeria Libera, Luca Bertini, Andrea Orecchini, Silvia Corezzi, Giorgio Schiro, Petra Pernot, Ralf Biehl, Caterina Petrillo, Lucia Comez, Cristiano De Michele, Alessandro Paciaroni
Summary: We investigated the stacking interactions and structural features of telomeric G4 multimers using a low-resolution structural approach that combines small-angle X-ray scattering (SAXS) with extremely coarse-grained (ECG) simulations. The self-assembly of G4 multimers leads to significant polydispersity and exponential distribution of contour lengths. We found that the strength of the stacking interaction between G4 monomers increases with increasing DNA concentration, as well as the average number of units in the aggregates. The proposed methodology may aid in the selection and design of drugs that target G4s under physiological conditions.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Haomiao Su, Jinglei Xu, Yuqi Chen, Qi Wang, Ziang Lu, Yage Chen, Kun Chen, Shaoqing Han, Zhentian Fang, Ping Wang, Bi-Feng Yuan, Xiang Zhou
Summary: This study reported a genome-wide strategy for identifying G4RPs and successfully identified a large number of G4RPs. Using this method, new G4 binding proteins were discovered, confirming the interaction of SERBP1 with G4. This developed a new strategy for studying the biological roles of nucleic secondary structures interacting with proteins in cells.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Valeria Libera, Francesca Ripanti, Caterina Petrillo, Francesco Sacchetti, Javier Ramos-Soriano, Maria Carmen Galan, Giorgio Schiro, Alessandro Paciaroni, Lucia Comez
Summary: Guanine-rich DNA sequences can form non-canonical nucleic acid structures called G-quadruplexes (G4s), which have implications in various fields. Ligands that interact with G4s have attracted attention for their potential in medical therapies and nanodevice applications. This study investigates the manipulation of the secondary structure of a human telomeric G4 sequence by two photosensitive ligands, demonstrating their different effects on G4 unfolding and stabilization.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Yihang Zhou, Yi Wang, Xiao Xiong, Arthur G. Appel, Chao Zhang, Xu Wang
Summary: Telomeres are composed of highly conserved simple tandem telomeric repeat motifs, which vary among different species. A fast Telomeric Repeats Identification Pipeline was developed and its accuracy was demonstrated in multiple species. The study reveals diverse telomeric repeat motifs in different insect species and rapid evolution of telomeres.
LIFE SCIENCE ALLIANCE
(2022)
Article
Biochemistry & Molecular Biology
Ming-Hao Hu, Jia-Hong Lin
Summary: This study proposed a strategy to design small-molecule ligands with selective binding to multimeric G-quadruplexes (G4s), and synthesized a library of multi-aryl compounds by attaching triazole rings to the quinoxaline skeleton. Among them, QTR-3 was identified as the most promising selective ligand that may bind at the G4-G4 interface, thereby stabilizing multimeric G4s and inducing DNA damage in the telomeric region, leading to cell cycle arrest and apoptosis. Importantly, QTR-3 exhibited more significant inhibition on breast cancer cells compared to normal mammary cells.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Chemistry, Multidisciplinary
Mingpan Cheng, Dehui Qiu, Liezel Tamon, Eva Istvankova, Pavlina Viskova, Samir Amrane, Aurore Guedin, Jielin Chen, Laurent Lacroix, Huangxian Ju, Lukas Trantirek, Aleksandr B. Sahakyan, Jun Zhou, Jean-Louis Mergny
Summary: Recent studies have shown that i-DNA, a four-stranded cytosine-rich DNA known as the i-motif, is formed in vivo. This study tested 271 different sequences and found that i-DNA stability is nearly independent on total spacer length, with the central spacer playing a special role in stability. The study also revealed that stability depends on the length of the C-tracts at both acidic and neutral pHs.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Poulomi Das, Khac Huy Ngo, Fernaldo Richtia Winnerdy, Arijit Maity, Blaz Bakalar, Yves Mechulam, Emmanuelle Schmitt, Anh Tuan Phan
Summary: This study investigates the adaptability of left-handed G4 structures towards the presence of bulges, presenting the structural characteristics of left-handed G4s accommodating varying numbers of bulges. Bulges in left-handed G4s exhibit distinct features compared to those in right-handed G4s, and elucidation of the intricate structural details may enhance understanding of the potential roles and limitations of these unique structures.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Arijit Maity, Fernaldo Richtia Winnerdy, Gang Chen, Anh Tuan Phan
Summary: Aberrant expansion of the hexanucleotide GGGGCC repeat in the human C9ORF72 gene is linked to ALS and FTD. The study shows that duplexes formed by G(4)C(2) repeats contain G center dot G pairs with different syn-anti base flipping dynamics, providing a basis for further research on the functions and targeting of these biologically relevant motifs.
Article
Biochemistry & Molecular Biology
Jean Chatain, Alain Blond, Anh Tuan Phan, Carole Saintome, Patrizia Alberti
Summary: Human telomeres contain GGGCTA variant motifs that show length-dependent instability, forming G4 and hairpin structures; RPA efficiently binds to G4 but poorly binds to hairpin structures of GGGCTA repeats, suggesting a potential mechanism for GGGCTA array instability.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Jielin Chen, Mingpan Cheng, Gilmar F. Salgado, Petr Stadlbauer, Xiaobo Zhang, Samir Amrane, Aurore Guedin, Fangni He, Jiri Sponer, Huangxian Ju, Jean-Louis Mergny, Jun Zhou
Summary: Research has shown that the addition of nucleotides in oligodeoxynucleotides forming intramolecular G4 structures favors the formation of a parallel fold, especially when added at the 5'end, known as the "flanking effect". This effect depends on loop arrangement and was confirmed through NMR experiments and molecular dynamics simulations.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Gitali Devi, Fernaldo Richtia Winnerdy, Jason Cheng Yu Ang, Kah Wai Lim, Anh Tuan Phan
Summary: This study investigates the formation of propeller loops spanning more than three layers in G-quadruplex structures. It was found that native nucleotide sequences are incompatible with this goal, but synthetic non-nucleotide linkers can be used to construct highly stable four-layered intramolecular parallel-stranded G4s. Control over loop design could enhance the engineering of G4-based nanoscaffolds for diverse applications.
Article
Biochemistry & Molecular Biology
Tiffany Rundstadler, Emmanuelle Mothes, Samir Amrane, Jean-Luc Stigliani, Pierre Verhaeghe, Genevieve Pratviel
Summary: G-quadruplex nucleic acids (G4s) are RNA and DNA secondary structures that regulate key biological processes and are potential targets for small molecule drugs. Gold(III) penta-cationic porphyrins, specific G4 ligands, can inhibit HIV-1 infectivity by interacting with G4s. A study on the structure/affinity relationship of gold(III) cationic porphyrins aims to identify the best candidate for functionalization and investigate the antiviral mechanism of action.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Krishnashish Bose, Arijit Maity, Khac Huy Ngo, J. Jeya Vandana, Neil A. Shneider, Anh Tuan Phan
Summary: This study visualizes the formation of higher-order structures by the G4C2 hexanucleotide repeat in the gene C9orf72, which is associated with amyotrophic lateral sclerosis and frontotemporal dementia. The researchers observed left-handed undulating G-wires with a periodicity of 4.4 nm and a uniform height in physiologically relevant conditions. These structures were resistant to degradation and could potentially accumulate in cells.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Julien Marquevielle, Aurore De Rache, Brune Vialet, Estelle Morvan, Jean-Louis Mergny, Samir Amrane
Summary: The Caenorhabditis elegans model has provided insights into the role of G-quadruplexes in genomic instability. Telomeric sequences in C. elegans show similarities to those in humans, but even small changes in these sequences can have significant effects on the folded G-quadruplex structure. This study determined the structure of the C. elegans telomeric sequence, revealing an intramolecular two G-tetrads basket type G-quadruplex structure with a C-T base pair in the diagonal loop. The findings shed light on the telomeric structure of the widely used C. elegans animal model.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Samir Amrane, Chloe Jaubert, Amina Bedrat, Tiffany Rundstadler, Patricia Recordon-Pinson, Cindy Aknin, Aurore Guedin, Aurore De Rache, Laura Bartolucci, Ibra Diene, Frederic Lemoine, Olivier Gascuel, Genevieve Pratviel, Jean-Louis Mergny, Marie-Line Andreola
Summary: The formation of G-quadruplex structures during HIV-1 infection plays a crucial role in viral replication and processing of viral RNA genome. The use of G4-binders has shown to efficiently inhibit HIV-1 infectivity.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Amani Kabbara, Brune Vialet, Julien Marquevielle, Pierre Bonnafous, Cameron D. D. Mackereth, Samir Amrane
Summary: COVID-19, SARS, and MERS are infectious diseases caused by coronavirus outbreaks. The identification of G-quadruplex structures in the coronavirus genomes suggests a potential new antiviral strategy by targeting RNA structures.
FRONTIERS IN CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Csaba Papp, Vineeth T. Mukundan, Piroon Jenjaroenpun, Fernaldo Richtia Winnerdy, Ghim Siong Ow, Anh Tuan Phan, Vladimir A. Kuznetsov
Summary: The composition of DNA sequences determines the structure and stability of G-quadruplexes (G4s). In this study, a large family of computationally defined and experimentally verified potential G4-B forming sequences (pG4-BS) was introduced. These sequences are preferentially localized in transcription regulatory regions and are associated with brain tissue, immune, and developmental processes. The ability of these sequences to form G4 structures was predicted with 91.5% accuracy in vitro.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Poulomi Das, Anh Tuan Phan
Summary: This study demonstrates that ligands specific for right-handed G4s do not bind specifically to left-handed G4s, as the presence of tight T-capping in left-handed G4s hinders access to the tetrads.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Kiran M. Patil, Danielle Chin, Hui Ling Seah, Qi Shi, Kah Wai Lim, Anh Tuan Phan
Summary: This study successfully used G4-PROTAC to targetly degrade the G4-binding protein RHAU/DHX36, providing a new approach to explore G4-protein networks and develop potential therapeutics.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Derrick Jing Yang Tan, Vee Vee Cheong, Kah Wai Lim, Anh Tuan Phan
Summary: A novel approach using tag phosphoramidites as adaptors enables enzymatic ligation of peptides and oligonucleotides, providing a simple and highly efficient method for the streamlined development and production of peptide/protein-oligonucleotide conjugates.
CHEMICAL COMMUNICATIONS
(2021)