Article
Biochemistry & Molecular Biology
Emil Laust Kristoffersen, Andrea Coletta, Line Morkholt Lund, Birgit Schiott, Victoria Birkedal
Summary: G-quadruplexes are noncanonical DNA structures that play important roles in DNA metabolic processes. We investigated the folding of consecutive G-quadruplexes in both potassium- and sodium-containing solutions and found coexistence of partially and fully folded DNA. Full consecutive G-quadruplex formation is inhibited by other DNA structures randomly nucleating on the DNA. Our study provides insights into the formation of consecutive G-quadruplexes in both equilibrium and nonequilibrium conditions.
NUCLEIC ACIDS RESEARCH
(2023)
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
Chemistry, Multidisciplinary
Diana Muller, Irene Bessi, Christian Richter, Harald Schwalbe
Summary: The folding kinetics of RNA G4 and DNA G4 differ significantly during K+-induced folding, mainly due to differences in their folded conformations, especially regarding the chi angle preferences. Modified DNA G4 can achieve faster folding kinetics and monomorphic conformations similar to RNA G4 by adjusting the chi angle.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Virology
Lu Lv, Leiliang Zhang
Summary: Monkeypox virus (MPXV), a member of Orthopoxvirus, has caused a Public Health Emergency of International Concern with a significant increase in cases and geographic range in 2022. This study aims to characterize the G-quadruplex (GQ) secondary structures encoded by MPXV and evaluate the binding and stabilization abilities of GQ ligands. The results demonstrate the presence of MPXV GQ and suggest GQs could be potential antiviral targets, providing a new approach for MPXV therapy.
JOURNAL OF MEDICAL VIROLOGY
(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
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
Chemistry, Applied
Fei Lu, Meng-Jia Zhang, Jun-Hui Li, Pei-Dan You, Lihong Liu, Chun-Qiong Zhou
Summary: Three new malachite green dimers were synthesized, and one of them exhibited selective NIR imaging towards human telomeric dimeric G-quadruplexes and excellent cytotoxicity.
Article
Chemistry, Multidisciplinary
Marco Campanile, Rosario Oliva, Pompea Del Vecchio, Roland Winter, Luigi Petraccone
Summary: LL-III, a natural anticancer peptide, has been found to bind to G-quadruplex structures with high affinity, which are known to be important targets in anticancer treatment.
CHEMICAL COMMUNICATIONS
(2023)
Review
Biochemical Research Methods
Yongsheng Li, Yunpeng Zhang, Tao Pan, Ping Zhou, Weiwei Zhou, Yueying Gao, Shaojiang Zheng, Juan Xu
Summary: Unrestrained cellular growth and immune escape in tumors are caused by incidental errors in the genome and transcriptome. Advances in next-generation sequencing have allowed the identification of genomic and transcriptomic aberrations, expanding the immunopeptidome. Understanding tumor microenvironments has been enhanced by new sequencing technologies and computational methods. Therefore, investigating tumor-specific antigens and the hidden proteome is crucial for developing effective immunotherapy targets for cancer.
BRIEFINGS IN BIOINFORMATICS
(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
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
Ying Bao, Xiaonong Zhang, Xiaoxuan Xiang, Yujing Zhang, Xinhua Guo
Summary: G-quadruplexes (G4s) are important molecules that regulate various physiological functions. Surface-enhanced Raman scattering (SERS) technique can quickly provide structural details of G4s and study their interactions with ligands. This study demonstrates that SERS is a powerful tool for revealing specific interactions between G4s and their ligands.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Editorial Material
Multidisciplinary Sciences
Igor G. Irastorza
Summary: Axions, hypothetical particles that could make up dark matter, could have their detection sensitivity improved by quantum manipulation technology.
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
Federica D'Aria, Bruno Pagano, Luigi Petraccone, Concetta Giancola
Summary: The study compares the thermodynamic stability of G4s formed by two different lengths of the KRAS promoter sequence, showing that the unfolding mechanism of KRAS 32R is more complex than that of KRAS 22RT. The binding properties of two well-known G4-targeting anticancer compounds, TMPyP4 and BRACO-19, to the KRAS G4s were also investigated. This physicochemical study aims to assist in selecting the best G4 target for potential anticancer drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Nunzia Iaccarino, Mingpan Cheng, Dehui Qiu, Bruno Pagano, Jussara Amato, Anna Di Porzio, Jun Zhou, Antonio Randazzo, Jean-Louis Mergny
Summary: The i-motif DNA, a non-canonical DNA secondary structure formed by cytosine-rich sequences, is of growing interest as a target in anticancer therapy. This study analyzed the CD and TDS spectra of 255 DNA sequences using multivariate data analysis to reveal unique spectral regions that could be diagnostic features in the analysis of i-DNA forming sequences.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biotechnology & Applied Microbiology
Olga Minenkova, Daniela Santapaola, Ferdinando Maria Milazzo, Anna Maria Anastasi, Gianfranco Battistuzzi, Caterina Chiapparino, Antonio Rosi, Giuseppe Gritti, Gianmaria Borleri, Alessandro Rambaldi, Clelia Dental, Cecile Viollet, Bruno Pagano, Laura Salvini, Emanuele Marra, Laura Luberto, Antonio Rossi, Anna Riccio, Emilio Merlo Pich, Maria Gabriella Santoro, Rita De Santis
Summary: A study has identified a human single chain antibody called 76clAbs that can block a key site on the SARS-CoV-2 spike protein, neutralize the Delta variant and other variants, and inhibit critical pathological features of COVID-19. Administered intranasally, it effectively combated infection in animal models. Therefore, 76clAbs may serve as a rapid and self-administrable early intervention tool independent of the immune status of SARS-CoV-2-infected individuals.
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
Cell Biology
Fabiana Napolitano, Sarah Di Somma, Giuliano Castellano, Jussara Amato, Bruno Pagano, Antonio Randazzo, Giuseppe Portella, Anna Maria Malfitano
Summary: G-quadruplexes are nucleic secondary structures characterized by G-tetrads. Combining G4 binders and oncolytic viruses in breast cancer cells can induce cell death and enhance cytotoxicity, suggesting a potential novel therapeutic approach for cancer treatment.
Article
Chemistry, Analytical
Antonella Miglione, Ada Raucci, Jussara Amato, Simona Marzano, Bruno Pagano, Tiziana Raia, Marco Lucarelli, Andrea Fuso, Stefano Cinti
Summary: This study developed an electrochemical printed strip for the detection of miRNA-29a at low levels, which showed good repeatability and selectivity. The research provides a way for the study and possible early diagnosis of Alzheimer's disease.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Roberta Rocca, Nicoletta Polera, Giada Juli, Katia Grillone, Annalisa Maruca, Maria Teresa Di Martino, Anna Artese, Jussara Amato, Bruno Pagano, Antonio Randazzo, Pietrosandro Tagliaferri, Pierfrancesco Tassone, Stefano Alcaro
Summary: RNA is currently a target of interest for the design of new small molecules with diverse pharmacological activities. Among these RNA molecules, long noncoding RNAs (lncRNAs) have been extensively associated with cancer pathogenesis. In particular, the overexpression of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays a crucial role in the development of multiple myeloma (MM). By utilizing the crystallographic structure of the triple-helical stability element of MALAT1, a structure-based virtual screening was conducted on a large commercial database, and five compounds were selected for in vitro assays. Among them, compound M5 showed the most promising results, destabilizing the MALAT1 triplex structure and demonstrating antiproliferative activity in MM cell models. M5 is suggested as a lead compound for further optimization to enhance its affinity towards MALAT1.
ARCHIV DER PHARMAZIE
(2023)
Article
Cell & Tissue Engineering
Maria Rosaria Ambrosio, Teresa Migliaccio, Fabiana Napolitano, Sarah Di Somma, Giovanni Maneli, Jussara Amato, Bruno Pagano, Antonio Randazzo, Giuseppe Portella, Pietro Formisano, Anna Maria Malfitano
Summary: In this study, the role of G4 motifs in adipogenic differentiation was investigated using human adipose-derived mesenchymal stem cells (ASCs). The results showed that G4 structures were increased in differentiated adipocytes compared to their precursors, and treatment with the G4 ligand Braco-19 reduced G4 content in the mature adipocytes. Furthermore, Braco-19 caused morphological changes and reduced lipid droplet formation and key gene expression in the mature adipocytes. These findings reveal a new role of G4 motifs in human adipocyte differentiation.
STEM CELL RESEARCH & THERAPY
(2023)
Review
Chemistry, Medicinal
Francesca Romano, Anna Di Porzio, Nunzia Iaccarino, Gelsomina Riccardi, Ritamaria Di Lorenzo, Sonia Laneri, Bruno Pagano, Jussara Amato, Antonio Randazzo
Summary: Modulation of G-quadruplex (G4) formation has been proposed as a powerful tool for cancer treatment through the control of oncogene expression. This review provides an overview of current knowledge on G4s in human oncogene promoters and the most representative G4-binding ligands. Targeting G4s has the potential to develop novel and highly specific anticancer drugs capable of selectively impacting gene expression.
EXPERT OPINION ON THERAPEUTIC PATENTS
(2023)
Article
Spectroscopy
Francesco D'Amico, Raffaele Graziano, Federica D'Aria, Pasquale Russomanno, Silvia Di Fonzo, Jussara Amato, Bruno Pagano
Summary: Epigenetic modifications of DNA and G-quadruplex structures are closely related and can be studied using UV resonance Raman spectroscopy. This study demonstrates that UVRR spectroscopy can detect spectral changes in G-quadruplex structures and indirectly identify modifications in guanine glycosidic conformations and changes induced by H-bond formation or hydration. These findings support the usefulness of UVRR spectroscopy for studying G-quadruplex structures in biologically relevant conditions.
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2023)
Article
Chemistry, Multidisciplinary
Federica Moraca, Simona Marzano, Francesco D'Amico, Antonio Lupia, Silvia Di Fonzo, Eleonora Vertecchi, Erica Salvati, Anna Di Porzio, Bruno Catalanotti, Antonio Randazzo, Bruno Pagano, Jussara Amato
Summary: In this study, three drugs were identified as potential binders to SARS-CoV-2 RNA G-quadruplex structures through ligand-based pharmacophore virtual screening.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Simona Marzano, Giulia Miglietta, Rita Morigi, Jessica Marinello, Andrea Arleo, Monica Procacci, Alessandra Locatelli, Alberto Leoni, Bruno Pagano, Antonio Randazzo, Jussara Amato, Giovanni Capranico
Summary: This study investigates the interplay between G4 affinity/selectivity, cytotoxicity, and immune gene activation in the search for new anticancer drugs. The researchers found that G4 affinity is critical for immune gene activation, but high cytotoxic potency interferes with it. The balance between G4 stabilization and cytotoxicity determines the level of immune gene activation in cancer cells, suggesting a new rationale for discovering effective anticancer G4 ligands based on low cell-killing potency and high immune stimulation.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Physical
Jussara Amato, Nunzia Iaccarino, Federica D'Aria, Francesco D'Amico, Antonio Randazzo, Concetta Giancola, Attilio Cesaro, Silvia Di Fonzo, Bruno Pagano
Summary: This study investigates the conformational equilibria of sequences forming noncanonical DNA structures in the promoter regions of important oncogenes BCL2 and KRAS, and their dependence on pH and cell-mimicking molecular crowding conditions. The results reveal that the i-motif structures in the promoters of BCL2 and KRAS are highly dynamic and exist in pH-dependent equilibrium with hairpin and hybrid i-motif/hairpin species. The study provides valuable insights into the factors that influence the molecular-level equilibrium between different conformational species involved in oncogene expression.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)
Article
Thermodynamics
Federica D'Aria, Bruno Pagano, Concetta Giancola
Summary: Cyclodextrins (CDs) have been shown to improve the stability, solubility, and bioavailability of various molecules, with low toxicity for different routes of administration. Isothermal titration calorimetry (ITC) is a key method for studying cyclodextrin/guest interaction, providing important thermodynamic parameters simultaneously.
JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY
(2022)