Article
Chemistry, Multidisciplinary
Jaroslav Malina, Hana Kostrhunova, Peter Scott, Viktor Brabec
Summary: The study demonstrates that a series of metallohelices bind to G4 DNA with high affinity, inhibit primer elongation catalyzed by Taq DNA polymerase, and downregulate the expression of c-MYC and c-KIT oncogenes in cells. These findings suggest that metallohelices hold promise as potential multitargeted drugs.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Dana Beseiso, Erin Chen, Sawyer E. McCarthy, Kailey N. Martin, Elizabeth P. Gallagher, Joanne Miao, Liliya A. Yatsunyk
Summary: G-quadruplexes (GQs) are DNA structures composed of stabilized G-tetrads. This study investigates telomeric DNA variants from Tetrahymena thermophila and solves the crystal structure of two variants, revealing new GQ structures. The results expand our understanding of telomeric repeats and GQs in general.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Jaroslav Malina, Hana Kostrhunova, Hualong Song, Peter Scott, Viktor Brabec
Summary: Some metallo-supramolecular helical assemblies that resemble short cationic alpha-helical peptides have been found to target and stabilize DNA G-quadruplexes (G4s) and downregulate G4-regulated genes in human cells. In this study, two pairs of asymmetric Fe(II) triplex metallohelices were investigated for their interaction with five different DNA G4s formed by human telomeric sequence and oncogenes' promoter regions. The metallohelices showed selective binding to G4s over duplex DNA and caused DNA polymerase arrest on G4-containing template strands. Furthermore, the investigated metallohelices suppressed the expression of c-MYC and k-RAS genes at mRNA and protein levels in HCT116 cancer cells.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(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
Pharmacology & Pharmacy
Andrea Criscuolo, Ettore Napolitano, Claudia Riccardi, Domenica Musumeci, Chiara Platella, Daniela Montesarchio
Summary: G-quadruplexes are important targets for anticancer/antiviral therapies. Over 3000 small-molecule ligands have been described, which exert their activity by damaging telomeres or altering gene expression in cancer cells and viruses. Detailed knowledge on the interactions between ligands and G-quadruplexes has been obtained through NMR and crystallographic studies.
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
Engineering, Environmental
Yakun Wang, Niping Chen, Zhenxing Pan, Zhaoyi Ye, Jiongpeng Yuan, Yaoxun Zeng, Wei Long, Wangqing Bian, Xiaojing Li, Kun Zhang, Yan He, Xujie Liu
Summary: This study presents the design and synthesis of a fluorescent probe SPN for detecting and stabilizing mtDNA G4s. The results show that SPN has a high sensitivity with a low detection limit and can effectively monitor G4s in cancer cells, indicating its potential applications in cancer diagnosis.
CHEMICAL ENGINEERING JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Sara Illodo, Cibran Perez-Gonzalez, Ramiro Barcia, Flor Rodriguez-Prieto, Wajih Al-Soufi, Mercedes Novo
Summary: Guanine quadruplexes (G4s) are four-stranded structures formed within guanine-rich DNA and RNA sequences that play a crucial role in biological processes. The recent discovery of G4 structures within mitochondrial DNA has brought significant advancements to the field. This study investigates the relevant G4 structures formed within CSB II and reveals the stability differences among different sequences.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
Chemistry, Multidisciplinary
Timo Hagen, Artur Laski, Anneke Bruemmer, Adam Pruska, Verena Schloesser, Antoine Clery, Frederic H-T Allain, Renato Zenobi, Sven Bergmann, Jonathan Hall
Summary: Gene expression is heavily influenced by RNA structure, with A-to-I editing activating latent rG4s and forming GI-quadruplexes, previously unrecognized structural motifs that may play a significant role in gene expression regulation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Anirban Ghosh, Eric Largy, Valerie Gabelica
Summary: This study focuses on using native mass spectrometry for drug screening on G-quadruplex DNA structures. By studying 28 sequences, a standardized screening method was established and recommendations for future research were provided. Furthermore, an R-based open-source application was developed to build and consult a database for further exploration.
NUCLEIC ACIDS RESEARCH
(2021)
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
Biochemistry & Molecular Biology
Phillip Wulfridge, Qingqing Yan, Nathaniel Rell, John Doherty, Skye Jacobson, Sarah Offley, Sandra Deliard, Kelly Feng, Jennifer E. Phillips-Cremins, Alessandro Gardini, Kavitha Sarma
Summary: CTCF is a critical regulator of genome architecture and gene expression. This study shows that R-loops and G-quadruplex structures facilitate CTCF binding and regulate chromatin organization. The stability of R-loops and G-quadruplex structures can affect CTCF occupancy and gene expression.
Article
Biochemical Research Methods
Sunny Y. Yang, David Monchaud, Judy M. Y. Wong
Summary: This article describes a G4-RNA-specific precipitation (G4RP) protocol for transcriptomic profiling of G4-RNAs. The method includes chemical cross-linking and affinity capture with a G4-specific probe, allowing comprehensive analysis of folded G4-RNAs. The protocol can be completed in 1-2 weeks and can be optimized for different experimental setups.
Review
Chemistry, Multidisciplinary
Jiantong Dong, Michael P. O'Hagan, Itamar Willner
Summary: G-Quadruplexes are of growing interest in biology, chemistry, nanotechnology, and material science. They have versatile applications as functional and structural motifs in DNA nanotechnology and material science, such as DNA switches, DNA machines, catalytic functions, dynamic networks, and nanoparticle assemblies. G-Quadruplex-modified nanomaterials have potential in nanomedicine.
CHEMICAL SOCIETY REVIEWS
(2022)
Article
Chemistry, Applied
Chun Wu, Jin-Biao Liu, Guodong Li, Suk-Yu Wong, Quan-Bin Han, Chung-Hang Leung, Dik-Lung Ma
Article
Chemistry, Medicinal
Ke-Jia Wu, Hai-Jing Zhong, Guodong Li, Chenfu Liu, Hui-Min David Wang, Dik-Lung Ma, Chung-Hang Leung
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Biochemistry & Molecular Biology
Pin-Hui Li, Li-Heng Liu, Cheng-Chung Chang, Rong Gao, Chung-Hang Leung, Dik-Lung Ma, Hui-Min David Wang
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2018)
Article
Biochemistry & Molecular Biology
Zhi-Peng Li, Hong-Bing Liu, Quan-Wei Zhang, Li-Feng Li, Wan-Rong Bao, Dik-Lung Ma, Chung-Hang Leung, Zhao-Xiang Bian, Ai-Ping Lu, Quan-Bin Han
Article
Chemistry, Analytical
Wanhe Wang, Chun Wu, Chao Yang, Guodong Li, Quan-Bin Han, Shengnan Li, Simon Ming-Yuen Lee, Chung-Hang Leung, Dik-Lung Ma
SENSORS AND ACTUATORS B-CHEMICAL
(2018)
Article
Chemistry, Analytical
Xiaomin Tang, Xiaotong Li, Dik-Lung Ma, Lihua Lu, Baohan Qu
Article
Chemistry, Multidisciplinary
Kasipandi Vellaisamy, Guodong Li, Chung-Nga Ko, Hai-Jing Zhong, Sarwat Fatima, Hiu-Yee Kwan, Chun-Yuen Wong, Wai-Jing Kwong, Weihong Tan, Chung-Hang Leung, Dik-Lung Ma
Review
Biochemistry & Molecular Biology
Chung-Hang Leung, Jia-Tong Zhang, Guan-Jun Yang, Hao Liu, Quan-Bin Han, Dik-Lung Ma
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Chemistry, Multidisciplinary
Bipin Kumar, Nuruzzaman Noor, Suman Thakur, Ning Pan, Harishkumar Narayana, Siu-cheong Yan, Faming Wang, Parth Shah
Review
Biochemistry & Molecular Biology
Ke-Jia Wu, Pui-Man Lei, Hao Liu, Chun Wu, Chung-Hang Leung, Dik-Lung Ma
Article
Chemistry, Medicinal
Shasha Cheng, Yi Kuang, Guodong Li, Jia Wu, Chung-Nga Ko, Wanhe Wang, Dik-Lung Ma, Min Ye, Chung-Hang Leung
Summary: This study reports the use of dehydroeburicoic acid (DEA) as a dual inhibitor of the Keap1-Nrf2 protein-protein interaction (PPI) and GSK3 beta, providing potential therapeutic strategies for alcoholic liver disease (ALD). DEA disrupts the Keap1-Nrf2 PPI and restores Nrf2 activity, leading to the activation of antioxidant genes. It also alleviates ethanol-induced mitochondrial dysfunction and exhibits minimal toxicity in the ALD cell model.
Review
Chemistry, Inorganic & Nuclear
Wanhe Wang, Jianhua Liu, Sang-Cuo Nao, Dik-Lung Ma, Jing Wang, Chung-Hang Leung
Summary: Changes in protein levels and types can indicate the occurrence of diseases, making differentially expressed proteins useful biomarkers for diagnosis and treatment. Luminescent iridium(III) complexes, especially affinity-based ones, with excellent optical properties, have gained attention in protein-based disease diagnostics. This review summarizes the current advances and future perspectives of affinity-based luminescent iridium(III) complexes for detecting disease-related proteins.
Article
Chemistry, Multidisciplinary
Ying Zhou, Shuofeng Yuan, Fan Xiao, Hongyan Li, Ziwei Ye, Tianfan Cheng, Cuiting Luo, Kaiming Tang, Jianpiao Cai, Jianwen Situ, Siddharth Sridhar, Wing-Ming Chu, Anthony Raymond Tam, Hin Chu, Chi-Ming Che, Lijian Jin, Ivan Fan-Ngai Hung, Liwei Lu, Jasper Fuk-Woo Chan, Hongzhe Sun
Summary: Understanding how host metal(loid)s regulate immune response is crucial for understanding the mechanism of infectious diseases. This study established a metal-coding system to analyze the links between metallome and COVID-19 pathogenesis and immunity. COVID-19 patients showed distinct metallome features compared to non-infected individuals, which could serve as biomarkers for disease diagnosis. Selenium was found to be strongly associated with interleukin-10 (IL-10), and selenium supplementation enhanced IL-10 expression in B cells while reducing proinflammatory cytokines in B and CD4+ T cells. Additionally, selenium supplementation alleviated lung damage in SARS-CoV-2-infected mice.
Article
Chemistry, Multidisciplinary
Yong Wang, Zhiguang Liang, Yuanyuan Zheng, Alan Siu-Lun Leung, Siu-Cheong Yan, Pui-Kin So, Yun-Chung Leung, Wing-Leung Wong, Kwok-Yin Wong
Summary: A series of isatin derivatives with different substituent groups were systematically designed and synthesized to study their inhibition of bacterial enzyme activity and antimicrobial potency. Modifying the substituent positions can maximize the antimicrobial potency and inhibitory action against the bacterial enzyme, leading to better understanding of the structure-activity relationship.
Article
Chemistry, Multidisciplinary
Zhiyuan Fang, Yanan Li, Yuanyuan Zheng, Xiaomei Li, Yu-Jing Lu, Siu-Cheong Yan, Wing-Leung Wong, Kin-Fai Chan, Kwok-yin Wong, Ning Sun