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, Multidisciplinary
Liu-Yi Liu, Tian-Zhu Ma, You-Liang Zeng, Wenting Liu, Zong-Wan Mao
Summary: This study reveals the structural basis for the specific recognition of G-quadruplex (G4) by pyridostatin (PDS) and its derivatives. The results demonstrate that the rigid aromatic rings of PDS linked by flexible amide bonds match adaptively with G-tetrad planes, enhancing p-p stacking and achieving specific recognition of G4s. The aliphatic amine side chains of PDS adjust conformation to interact with the phosphate backbone via hydrogen bonding and electrostatic interactions, increasing affinity for G4s.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Conner L. Olson, Alexandra T. Barbour, Thomas A. Wieser, Deborah S. Wuttke
Summary: G-quadruplexes (G4s) are stable secondary structures that form in guanine-rich regions of single-stranded nucleic acids and pose challenges for DNA maintenance. The proteins Replication Protein A (RPA) and CTC1-STN1-TEN1 (CST) are involved in managing G4s at telomeres. RPA tightly binds telomeric G4s, while CST's ability to bind G-rich ssDNA is inhibited by the presence of G4s. RPA's greater cellular abundance and its collaborative DNA-binding domains suggest that it may be the primary protein complex responsible for resolving G4s at telomeres.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Anurag Noonikara-Poyil, Alvaro Munoz-Castro, H. V. Rasika Dias
Summary: This study describes the isolation and full characterization of a thermally stable, copper(I) acetylene complex using a highly fluorinated bis(pyrazolyl)borate ligand support, as well as the details of a related copper(I) complex. Raman data show significant red-shifts in C equivalent to C stretch of different alkynes bound to copper(I), with computational analysis indicating that the interaction is primarily of the electrostatic character. The study also highlights the catalytic activity of a mononuclear copper complex in [3 + 2] cycloadditions and compares its effectiveness with a trinuclear copper catalyst.
Article
Multidisciplinary Sciences
Ahyun Son, Veronica Huizar Cabral, Zijue Huang, Theodore J. Litberg, Scott Horowitz
Summary: Recent research has found that G-quadruplex (G4) nucleic acids are effective in preventing protein aggregation and improving protein folding in Escherichia coli. Through in vitro protein folding experiments, it was discovered that G4s can accelerate protein folding by rescuing kinetically trapped intermediates. Time-course folding experiments in E. coli further showed that G4s primarily enhance protein folding quality instead of preventing protein aggregation. This study suggests that nucleic acids and ATP-independent chaperones may play important roles in determining the folding fate of proteins.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Chao Gao, Jieya Deng, Naureen Anwar, Muhammad Umer, Jixin Chen, Qiao Wu, Xingxing Dong, Hua Xu, Yi He, Zhangqian Wang
Summary: The effect of molecular crowding on the conformation of G-quadruplexes was investigated in this study. Molecular crowding did not induce parallel structures in the explored model sequences, but promoted the formation of G-quadruplex aggregates and looser monomer structures. Molecular crowding also inhibited the interaction between ligands and parallel structured G-quadruplexes.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Alessio Cantara, Yu Luo, Michaela Dobrovolna, Natalia Bohalova, Miroslav Fojta, Daniela Verga, Lionel Guittat, Anne Cucchiarini, Solene Savrimoutou, Cecile Haberli, Jean Guillon, Jennifer Keiser, Vaclav Brazda, Jean Louis Mergny
Summary: Parasitic helminths infecting humans and cattle have significant impacts on health and livestock production. This study identified and compared G4 sequences in the genomes of various helminths and found that a Nematode species, Ascaris lumbricoides, had a high enrichment of stable G4 structures. Experimental confirmation of G4 formation and the discovery of small molecules that can selectively recognize and bind G4 motifs in a parasitic helminth demonstrate the potential for targeting G4 structures in the treatment of helminth infections.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Chemistry, Medicinal
Tiago Santos, Gilmar F. Salgado, Eurico J. Cabrita, Carla Cruz
Summary: This article discusses the progress in the design of G-quadruplex binding ligands and the various methods available to assess the binding interactions. Different experimental approaches, such as structure-based, affinity-based, and high-throughput methods, each have their unique advantages and drawbacks. The combination of these techniques has led to the discovery of numerous G4 ligands for diagnostic and therapeutic purposes.
Article
Biochemistry & Molecular Biology
Evangelos Balanikas, Lara Martinez-Fernandez, Gerard Baldacchino, Dimitra Markovitsi
Summary: This study investigates the generation of electron holes in G-Quadruplexes upon ionization by low-energy UV photons, using quantum chemistry calculations and time-resolved absorption spectroscopy. It demonstrates that the position of the electron hole is determined by the location of adenine groups at the ends, impacting the electronic absorption spectrum of (G(+))(.) radical cations. The decay of these radicals is found to be highly anisotropic, with a fast process followed by a slower one, leading to deprotonation and the formation of reaction products absorbing in the 300-500 nm spectral domain.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Jing-Tao Zhang, Li-Xia Wang, Feng-Min Yang, Luo Yang, Yan Liu, Ya-Lin Tang
Summary: A new type of N-containing alkaloids, 3,8a-disubstituted indolizinones, have been reported with their substituent effects targeting DNA c-myc G-quadruplex. The ability of substrate I8, 3-naphtyl-8a-(pyridin-2-yl), in targeting DNA parallel G-quadruplexes in vitro was investigated as an example.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Ilias Georgakopoulos-Soares, Guillermo E. Parada, Hei Yuen Wong, Ragini Medhi, Giulia Furlan, Roberto Munita, Eric A. Miska, Chun Kit Kwok, Martin Hemberg
Summary: This study reveals the enrichment of G4 motifs near splice junctions, suggesting their regulatory role in RNA stability and splicing. G4 motifs play important roles in exon skipping and inclusion, and are associated with multiple RNA binding proteins. Furthermore, G4 motifs show strong enrichment at splice sites in mammals and birds, indicating the evolutionary conservation of this splice regulatory mechanism.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Alexa M. Salsbury, Haley M. Michel, Justin A. Lemkul
Summary: This study used polarizable simulations to investigate telomeric DNA structures, including G-quadruplexes and G-hairpins. The presence of specific motifs, such as the G-triad, in the telomeric G-quadruplex suggests potential druggable sites. In addition, the simulations showed the unbiased formation of G-triad and G-tetrad in the G-hairpin, and the involvement of cations in their formation. Furthermore, the study demonstrated the specific interactions between K+ ions and guanine bases, providing new insights into the influence of ions on telomeric DNA structures.
Article
Biochemistry & Molecular Biology
Anup Pandith, Upendra Nagarajachari, Ravi Kumara Guralamatta Siddappa, Sungjin Lee, Chin-Ju Park, Krishnaveni Sannathammegowda, Young Jun Seo
Summary: This study reports simple pyridinium and quinolinium salts for the selective recognition of G-quadruplexes (G4s), among which probe 1 selectively discriminates parallel G4s from anti-parallel/hybrid G4s at pH 7.2 through significant changes in absorption and emission spectra. The symmetrical molecular configuration in probe 1 enhances intramolecular charge transfer and allows for highly effective disaggregation in the presence of parallel G4-forming ODNs. The study provides insights for future design of selective compounds targeting parallel G4s, confirmed through various spectroscopic and simulation studies.
BIOORGANIC & MEDICINAL CHEMISTRY
(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
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
Chemistry, Multidisciplinary
Susanta Haldar, Yashu Zhang, Ying Xia, Barira Islam, Sisi Liu, Francesco L. Gervasio, Adrian J. Mulholland, Zoe A. E. Waller, Dengguo Wei, Shozeb Haider
Summary: In this study, the mechanism of TMPyP4-induced RNA G-quadruplex (G4) unfolding was investigated using computational simulations and biophysical experiments. The results revealed that TMPyP4 interacts with RNA G4 through groove binding and top-face binding, disrupting hydrogen bonds between nucleotides.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Anamaria Trandafir, G. Dan Pantos, Adelina Ilie
Summary: This study reports a new approach to synthesize hybrid carbon-boron nitride networks using custom-designed molecular precursors and their ability to assemble on a surface. Through scanning tunneling microscopy and density functional theory simulations, the study demonstrates the hierarchical hydrogen-bonded assembly of chiral homodimers as building blocks for 2D networks. The study also shows that this network material can be doped with sodium atoms to modulate its electronic structure and transport properties.
Article
Optics
Lukas Ohnoutek, Ji-Young Kim, Jun Lu, Ben J. Olohan, Dora M. Rasadean, G. Dan Pantos, Nicholas A. Kotov, Ventsislav K. Valev
Summary: The study demonstrates the third-harmonic Mie scattering optical activity in suspensions of semiconductor nanostructured helices, allowing for chiroptical characterization of sample volumes as small as 10(-17) m(3). The new experimental results open up possibilities for high-throughput chiroptical characterization of chiral compounds in ultrasmall volumes.
Article
Biochemistry & Molecular Biology
Marianna Martella, Flavia Pichiorri, Rupesh Chikhale, Mahmoud A. S. Abdelhamid, Zoe A. E. Waller, Steven S. Smith
Summary: Concatemers of d(TCCC) are found throughout the human genome and can cause deletions at the RACK7 locus. They form G-quadruplexes for d(GGGA)(n) sequences with n > 3, and i-motif structures for d(TCCC)(n) sequences at neutral pH with n >= 7. Deletions in the PC3 cell line only occur when the d(TCCC)(n) variant forms unresolved i-motif structures at neutral pH.
NUCLEIC ACIDS RESEARCH
(2022)
Editorial Material
Chemistry, Multidisciplinary
Calvin Chau, Sajal Sen, Adam C. Sedgwick, Philip A. Gale, G. Dan Pantos, Sung Kuk Kim, Jung Su Park, Elisa Tomat, Jonathan F. Arambula, Anne E. Gorden, Hiroyuki Furuta
Summary: This article celebrates Professor Jonathan Sessler's 65th birthday by tracing his life and career path. It highlights his early days as an independent researcher and his contributions to the field of chemistry. The article aims to inspire readers to pursue their academic endeavors and emphasizes Jonathan's guiding motto.
Article
Biochemistry & Molecular Biology
Kelly L. Irving, Jessica J. King, Zoe A. E. Waller, Cameron W. Evans, Nicole M. Smith
Summary: DNA is capable of forming alternative secondary structures, including the i-motif, which was previously believed to be unstable in cellular environments. Recent studies have shown the existence of i-motifs in the human genome and their role in gene regulation. This review discusses the effects of epigenetic modifications on i-motif structure, factors influencing i-motif formation in cells, and highlights the recent progress in targeting i-motifs for biotechnology and therapeutic purposes.
Article
Chemistry, Medicinal
Rupesh V. Chikhale, Dilek Guneri, Robert Yuan, Christopher J. Morris, Zoe A. E. Waller
Summary: There are very few compounds known to interact with i-motif (iM) DNA, but sugar-containing molecules show potential to target these structures. This study assessed the interaction properties of the sugar-containing natural products baicalin and geniposidic acid with iM-DNA, and found that they could potentially serve as probes for studying the structure and function of i-motif forming DNA sequences.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Samuel R. Clowes, Dora M. Rasadean, Tiberiu-M. Gianga, Tamas Javorfi, Rohanah Hussain, Giuliano Siligardi, G. Dan Pantos
Summary: Cyanine dyes can form H- and J-aggregates in water. We discovered that the cyanine dye S0271 can assemble into vortex-induced chiral J-aggregates in water. The chirality of the J-aggregates is determined by the directionality of the vortex. This study used conventional benchtop CD spectropolarimeters and Mueller matrix polarimetry to analyze the aggregates.
Article
Biochemistry & Molecular Biology
Ahmed A. Ahmed, William Greenhalf, Daniel H. Palmer, Nicole Williams, Jenny Worthington, Tariq Arshad, Shozeb Haider, Effrosyni Alexandrou, Dilek Guneri, Zoe A. E. Waller, Stephen Neidle
Summary: The naphthalene diimide compound QN-302 exhibits high anti-proliferative activity in pancreatic cancer cell lines and anti-tumor activity in several experimental models for the disease. It downregulates the expression of S100P gene and protein, which is involved in key pathways in human cancers and has been identified as a potential biomarker in pancreatic cancer.
Article
Chemistry, Multidisciplinary
Hanna K. Maliszewska, Mahmoud A. S. Abdelhamid, Maria J. Marin, Zoe A. E. Waller, Maria Paz Munoz
Summary: The constant need for new drugs has led to the exploration of alternative structures in medicinal and pharmaceutical chemistry. Organometallic compounds, particularly gold carbenes, have shown great potential as metallodrugs for important organic reactions and as antimicrobial, antifungal, and anticancer agents. This study focuses on the synthesis of new metallodrugs by combining bis(pyridyl)allenes and metal complexes, and highlights the promising anticancer activity of gold carbene complexes against breast cancer cells, as well as their interactions with DNA.
PURE AND APPLIED CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Sophie L. Williams, Corella S. Casas-Delucchi, Federica Raguseo, Dilek Guneri, Yunxuan Li, Masashi Minamino, Emma E. Fletcher, Joseph T. P. Yeeles, Ulrich F. Keyser, Zoe A. E. Waller, Marco Di Antonio, Gideon Coster
Summary: This study investigates the effects of physiological quadruplex secondary structures on genome stability by reconstituting eukaryotic DNA replication in vitro. G-quadruplexes (G4s) and intercalated Motifs (iMs) are found to form during replication and thereby induce replisome stalling, leading to helicase-polymerase uncoupling and nascent DNA breakage. A single physiological G4 or iM structure stalls the eukaryotic replisome by inhibiting leading strand synthesis. Helicase-polymerase uncoupling occurs following replication stalling at G4s. iMs can induce breakage on nascent DNA. Stalled forks at G4s or iMs can be rescued by the accessory helicase Pif1. In vitro reconstitution shows that a single physiological G4 or iM secondary structure stalls the eukaryotic replisome by inhibiting leading strand synthesis.
Article
Biochemistry & Molecular Biology
Samuel R. Clowes, Yusuf Ali, Olivia R. Astley, Dora M. Rasadean, G. Dan Pantos
Summary: G-quadruplexes (G4s) are potential alternative targets for chemotherapy. In this study, a series of compounds derived from beta-amino acids were screened against oncogenic G4 sequences. The effect of point chirality on G4 stabilization was investigated using three sets of enantiomers. Enantioselective binding behavior was observed and docking studies and UV-vis titrations were used to understand this selective binding behavior.
Article
Chemistry, Organic
Effrosyni Alexandrou, Dilek Guneri, Stephen Neidle, Zoe A. E. Waller
Summary: GC-rich sequences can fold into G-quadruplexes and i-motifs, which play a role in gene expression. QN-302, an experimental anticancer drug, down-regulates cancer-related genes and destabilizes i-motif DNA structures. The study suggests that G-quadruplexes and i-motifs should be considered as a dynamic DNA system.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Hanna K. Maliszewska, Carla Arnau del Valle, Ying Xia, Maria J. Marin, Zoe A. E. Waller, Maria Paz Munoz
Summary: This study explores the incorporation of donor-type substituents on the allene core to form coordination complexes, discussing their potential applications in catalysis and interaction with chemical and biological systems. It also demonstrates the synthesis and characterization of bis(pyridyl)allenes as novel Pd(ii), Pt(iv), and Au(iii) complexes, and their use as catalysts and antimicrobial or anticancer agents with promising activities. Additionally, the study delves into their unusual interaction with DNA structures, opening up new avenues for research in metallodrugs with new mechanisms of action.
DALTON TRANSACTIONS
(2021)
Article
Chemistry, Multidisciplinary
Susanta Haldar, Yashu Zhang, Ying Xia, Barira Islam, Sisi Liu, Francesco L. Gervasio, Adrian J. Mulholland, Zoe A. E. Waller, Dengguo Wei, Shozeb Haider
Summary: The cationic porphyrin TMPyP4 can stabilize different topologies of DNA G4 structures via multiple binding modes, but can have both stabilizing and destabilizing effects on RNA G4 structures. The mechanism of TMPyP4-induced RNA G4 unfolding involves a two-state interaction mechanism with groove-bound and top-face-bound conformations. TMPyP4 disrupts Hoogsteen H-bonds between guanine bases and intercalates between the top-to-bottom G-tetrads, revealing a strong correlation between computational and experimental approaches.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
