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
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
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
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
Cell Biology
Shalu Sharma, Ananda Kishore Mukherjee, Shuvra Shekhar Roy, Sulochana Bagri, Silje Lier, Meenakshi Verma, Antara Sengupta, Manish Kumar, Gaute Nesse, Deo Prakash Pandey, Shantanu Chowdhury
Summary: The study reveals that the telomere-repeat-binding-factor TRF2 binds to G-quadruplexes in the hTERT promoter, leading to H3K27 trimethylation and repression of hTERT in both cancer and normal cells. Two highly recurrent hTERT promoter mutations found in many cancers disrupt G-quadruplexes, resulting in loss of TRF2 binding.
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
Biochemistry & Molecular Biology
Sampat N. Satapathy, Partha S. Nial, Kiran D. Tulsiyan, Umakanta Subudhi
Summary: Recently, the importance of light rare earth elements (LREEs) in modern technologies has increased. This study discovered the formation of G-quadruplex in human telomeric variants in the presence of micromolar concentrations of LREEs. The results suggest a binding stoichiometry of 2:1 between lanthanide ions and telomeric variants, with LREE ions coordinating between adjacent G-quartets.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2024)
Article
Biochemistry & Molecular Biology
Xueyu Hao, Chunyu Wang, Yu Wang, Chunjie Li, Jingwei Hou, Feng Zhang, Chuanqing Kang, Lianxun Gao
Summary: Topological conversion of human telomeric G-quadruplex induced by naphthalene diimide (NDI) ligands in K+ solution was discovered, where hybrid-type GQs were selectively induced to highly stable parallel-type GQs. This finding will inspire further studies on ligand design with GQ conformational regulation functions and nanotechnological systems based on nucleic acids regulating GQ conformation dynamically.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Xiaobin Ling, Yuqi Yao, Lei Ding, Jinbiao Ma
Summary: The study reveals that the nucleic acid binding protein UP1 can bind and unfold the G-quadruplexes in human telomere DNA. The RNA recognition motifs RRM1 and RRM2 in UP1 are responsible for initial binding, unfolding, and completion of G-quadruplexes unfolding, respectively. The TAG binding motif in the telomeric G-quadruplex Loop2 is critical for UP1 recognition and initiation of G-quadruplexes unfolding.
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
(2023)
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, Medicinal
Alberto Ongaro, Giovanni Desiderati, Erika Oselladore, Davide Auricchio, Maurizio Memo, Giovanni Ribaudo, Claudia Sissi, Alessandra Gianoncelli
Summary: This study found that guanine-rich sequences can form G-quadruplex structures in oncogenes and telomeres, inhibiting immortalization of cancer cells. Researchers improved ligand design based on an anthraquinone scaffold using click chemistry to enhance side chain length and interactions with nucleobases, leading to increased stability and selectivity towards G4 DNA.
Article
Chemistry, Organic
Daniele Malpicci, Stefano Andolina, Stefano Di Ciolo, Elena Lucenti, Elena Cariati, Simona Marzano, Bruno Pagano, Jussara Amato, Antonio Randazzo, Clelia Giannini
Summary: This study reports the synthesis and characterization of a small series of cyclic triimidazole derivatives functionalized with methylated pyridine or guanidine moieties, and their ability to bind to G-quadruplexes. Some of these compounds exhibited high affinity and effective G-quadruplex-stabilizing properties, indicating their potential as leads for developing more potent analogues.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
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
Biochemical Research Methods
Yue Wang, Guo Li, Tong Meng, Lin Qi, Hui Yan, Zhiguo Wang
Summary: The designed monohydrazone derivative shows specific preference in binding and stabilizing parallel human telomeric G4. The end-stacking binding mode is preferred, with van der Waals interactions playing a leading role in determining binding affinity. These findings support the design of novel selective stabilizers targeting telomeric G4s.
JOURNAL OF MOLECULAR GRAPHICS & MODELLING
(2022)
