Article
Chemistry, Multidisciplinary
Liu-Yi Liu, Tian-Zhu Ma, You-Liang Zeng, Wenting Liu, Hang Zhang, Zong-Wan Mao
Summary: A novel class of G4-binding organic-platinum hybrids, L-1-cispt and L-1-transpt, were designed with spatial matching for G4 binding and G4 DNA reactivity for binding site locking. The study revealed that L-1-cispt and L-1-transpt mediated genomic dysfunction could activate the RIG-I pathway and induce immunogenic cell death. In vivo experiments demonstrated that using L-1-cispt/L-1-transpt-treated cells as therapeutic vaccines stimulated a robust immune response and effectively inhibited tumor growth. These findings highlight the importance of rational combination of spatial recognition and covalent locking in G4-targeting drug design and their potential in immunotherapy.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Aishwarya Muruganantham, Arokya Nithya Deva Sahayam, Soundarapandian Suganthi, Aleyamma Alexander, Archana Sumohan Pillai, Israel V. M. V. Enoch
Summary: DNA forms non-canonical Guanine-rich-quadruplex structures that play crucial roles in cellular processes. Selective binding and stabilization of these structures with small molecular ligands are important for controlling cell proliferation and developing therapeutics. This study reports the synthesis of a complex and its evaluation of binding interactions with various DNAs.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
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
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
Zhe Shen, Ruiling Zheng, Huamao Yang, Sunhui Xing, Xiangxiang Jin, Hao Yan, Jufan Zhu, Yanan Mei, Feng Lin, Xiaohui Zheng
Summary: This study explores the biological effects of G-quadruplex stabilizer Tetra-Pt(bpy) in telomerase-positive cancer cells, revealing its ability to accelerate telomere shortening, inhibit cell proliferation, induce senescence, decrease cell migration, and suppress FAK transcription. Tetra-Pt(bpy) also shows potential as a novel chemotherapeutic agent for targeting telomerase-positive cancer cells.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(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
Wenxuan Hu, Haitao Jing, Wenqiang Fu, Zengrong Wang, Jiang Zhou, Na Zhang
Summary: In this study, a new type of G-quadruplex structure, parallel homomeric bimolecular G-quadruplex, was demonstrated to undergo strand displacement reaction with short G-rich DNA fragments at room temperature, resulting in the formation of a parallel heteromeric trimolecular G-quadruplex. This provides new insights into the development of complex architectures in G-quadruplex-based DNA nanotechnology.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biotechnology & Applied Microbiology
Vaclav Brazda, Otilia Porubiakova, Alessio Cantara, Natalia Bohalova, Jan Coufal, Martin Bartas, Miroslav Fojta, Jean-Louis Mergny
Summary: The study identified multiple potential G-quadruplex forming sequences in the G4-EA-H1N1 genomes, which could serve as potential therapeutic targets.
Review
Biochemistry & Molecular Biology
Huiling Shu, Rongxin Zhang, Ke Xiao, Jing Yang, Xiao Sun
Summary: G-quadruplexes are non-canonical secondary nucleic acid structures that play important roles in genome regulation. Interactions between G-quadruplexes and proteins have diverse biological functions and potential therapeutic applications.
Article
Biochemical Research Methods
Marco Caterino, Katrin Paeschke
Summary: The nucleic acid structure known as G-quadruplex (G4) plays a significant role in nucleic acid-based mechanisms that impact cellular processes. DNA G4 is well-studied, while RNA G4 is gaining attention for its role in cellular homeostasis. Proper regulation of G4 structures within cells is crucial, and helicases are important in resolving them. However, only a few rG4 unwinding helicases have been identified and characterized so far.
Article
Biochemistry & Molecular Biology
Samar Ali, Emilia Puig Lombardi, Deepanjan Ghosh, Tao Jia, Geraldine Vitry, Lina Saker, Joel Poupon, Marie-Paule Teulade-Fichou, Alain Nicolas, Arturo Londono-Vallejo, Sophie Bombard
Summary: Pt-ttpy shows dual targeting efficiency on DNA by inducing telomere dysfunction and genomic DNA damage at specific loci, while not particularly accumulating in potential G4 forming sequences.
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.
Review
Genetics & Heredity
Fangyuan Li, Jiang Zhou
Summary: Non-coding RNAs (ncRNAs), particularly lncRNAs and miRNAs, play a significant role in gene expression regulation, and their interplay with proteins and other RNAs is mediated by higher-order structures such as RNA G-quadruplexes (rG4s). The formation of rG4s, which are predicted in guanine-rich sequences, is closely associated with various human diseases. Understanding the dynamic balance between rG4s and RNA stem-loop/hairpin structures, as well as the interaction between ncRNAs and interactors, is crucial for modulating gene expression and disease progression. The folding of ncRNAs into the appropriate three-dimensional structure is of critical importance and opens up new therapeutic possibilities for diseases associated with potential-G4-containing-ncRNAs.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2023)
Article
Biochemistry & Molecular Biology
Yan Zhang, Zhidong Qiu, Ming Zhu, Ye Teng
Summary: Compound K (CK), a major metabolite of Panax ginseng, has been shown to enhance the formation of G-quadruplexes (G4s) and stabilize them through electrostatic interactions. This in turn, leads to the regulation of transcription involving G4-containing templates, resulting in reduced full-length transcripts and decreased transcription efficiency. These findings provide new insights into the pharmacological study of ginsenosides at the gene level.
Article
Biochemistry & Molecular Biology
Hijiri Hasegawa, Ikkei Sasaki, Kaori Tsukakoshi, Yue Ma, Kazuo Nagasawa, Shusuke Numata, Yuuki Inoue, Yeji Kim, Kazunori Ikebukuro
Summary: Genomic DNA methylation is studied as a potential biomarker for disease diagnosis. This study focuses on detecting CpG methylation in G4-forming oligonucleotides using G4 ligands, which show significant differences in fluorescence and chemiluminescence intensities between methylated and unmethylated DNAs. This research provides a new method for detecting DNA methylation based on structural changes using G4 ligands.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Valentin Fuchs, Klaudia Cseh, Michaela Hejl, Petra Vician, Benjamin Neuditschko, Samuel M. Meier-Menches, Lukas Janker, Andrea Bileck, Natalie Gajic, Julia Kronberger, Martin Schaier, Sophie Neumayer, Gunda Koellensperger, Christopher Gerner, Walter Berger, Michael A. Jakupec, Michael S. Malarek, Bernhard K. Keppler
Summary: A series of highly lipophilic Cp-substituted molybdenocenes with different bioactive chelating ligands were synthesized and characterized. They showed significantly increased cytotoxic potency compared to non-Cp-substituted counterparts. In vivo experiments demonstrated tumor growth inhibition for the most active complex containing the thioflavone ligand, along with significant regulation of tubulin-associated and mitochondrial inner membrane proteins.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Analytical
Olga V. Kuznetsova, Bernhard K. Keppler, Andrei R. Timerbaev
Summary: This study developed a unified protocol for the preparation of seawater samples for ICP-MS analysis of nanoparticles, which involved acidification and ultrafiltration to stabilize the particles and facilitate metal analysis. High-resolution ICP-MS method was used to achieve very low limits of detection.
Article
Pharmacology & Pharmacy
Janos P. Meszaros, Wolfgang Kandioller, Gabriella Spengler, Alexander Prado-Roller, Bernhard K. Keppler, Eva A. Enyedy
Summary: This study introduces half-sandwich Rh complexes that can be activated in the acidic, extracellular pH of tumor tissue, reducing the side effects and improving the efficacy of chemotherapy.
Article
Chemistry, Organic
Pablo Corton, Natalia Fernandez-Labandeira, Mauro Diaz-Abellas, Carlos Peinador, Elena Pazos, Arturo Blanco-Gomez, Marcos D. Garcia
Summary: A new polycationic pseudo[1]rotaxane was successfully synthesized through hydrazone bonds, self-assembled in excellent yield in aqueous media. The thermodynamically controlled process involves the [1 + 1] reaction of a bisaldehyde and a trishydrazine, formation of the macrocyclic part, conversion into pseudo[1]rotaxane, and the one-pot [1 + 1 + 1] condensation process. The obtained molecule exhibited the ability to form self-inclusion complexes and supramolecular aggregates in different concentration ranges.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Yvonne Lerchbammer-Kreith, Michaela Hejl, Petra Vician, Michael A. Jakupec, Walter Berger, Mathea S. Galanski, Bernhard K. Keppler
Summary: Based on their drug delivery properties and activity against tumors, PAMAM dendrimers were combined with platinum(IV) complexes to improve anticancer treatment. The conjugates showed faster reduction behavior compared to the platinum(IV) complexes and exhibited significantly increased cytotoxic activity in human cell lines. In vivo experiments demonstrated tumor growth inhibition and prolonged animal survival.
Article
Chemistry, Multidisciplinary
Martin Schaier, Sarah Theiner, Dina Baier, Gabriel Braun, Walter Berger, Gunda Koellensperger
Summary: In this study, a workflow combining low-dispersion laser ablation with inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-TOFMS) was presented, enabling spatial single-cell metallomics in tissue to decode cellular heterogeneity. The toolbox of single-cell metallomics was expanded by integrating the concepts of imaging mass cytometry (IMC) to utilize metal-labeled antibodies for cellular tissue profiling.
Article
Chemistry, Multidisciplinary
Alexander Kastner, Hemma Schueffl, Patrick A. Yassemipour, Bernhard K. Keppler, Petra Heffeter, Christian R. Kowol
Summary: Platinum(IV) prodrugs are promising alternatives to platinum(II) anticancer therapeutics. This study investigated the reactivity and synthetic usability of a platinum(IV) complex with hydrolyzable equatorial ligands, and successfully synthesized stable platinum(IV) complexes suitable for long-circulating tumor-targeting strategies. Additionally, platinum(IV) complexes with equatorial maleimides were synthesized, showing prolonged plasma half-life and improved anticancer activity compared to oxaliplatin.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Correction
Oncology
Mathea Sophia Galanski, Bernhard K. K. Keppler
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Monika Caban, Bettina Koblmueller, Diana Groza, Hemma H. Schueffl, Alessio Terenzi, Alexander Tolios, Thomas Mohr, Marlene Mathuber, Kushtrim Kryeziu, Carola Jaunecker, Christine Pirker, Bernhard K. Keppler, Walter Berger, Christian R. Kowol, Petra Heffeter
Summary: Through chemical modifications, KP2187 has similar activity and action as other clinically used EGFR inhibitors, without interfering with EGFR binding. In vitro and in vivo experiments have shown that KP2187 can significantly inhibit tumor cell proliferation and activate the EGFR signaling pathway. Moreover, KP2187 has a high synergistic effect with VEGFR inhibitors, indicating its potential as a hypoxia-activated prodrug.
Article
Chemistry, Applied
Alexia Tialiou, Zahraa H. Athab, Robert T. Woodward, Veronika Biegler, Bernhard K. Keppler, Ahmed F. Halbus, Michael R. Reithofer, Jia Min Chin
Summary: A novel hydroxypropyl cellulose (gHPC) hydrogel with graded porosity was successfully synthesized by cross-linking different parts of the hydrogel at different temperatures. The pore size in the hydrogel decreased from top to bottom. The hydrogel also showed graded mechanical properties, with the top layer being able to withstand 50% compression before fracture, while the middle and bottom layers could withstand 80% compression.
CARBOHYDRATE POLYMERS
(2023)
Article
Cell Biology
Livia Gruber, Maximilian Jobst, Endre Kiss, Martina Karasova, Bernhard Englinger, Walter Berger, Giorgia Del Favero
Summary: Bladder cells rely on the cytoskeletal network and endoplasmic reticulum (ER) to maintain mechanical stability. The rearrangement of ER can lead to changes in cellular mechanical properties.
CELL COMMUNICATION AND SIGNALING
(2023)
Correction
Biochemistry & Molecular Biology
Mathea Sophia Galanski, Michael A. Jakupec, Bernhard K. Keppler
CURRENT MEDICINAL CHEMISTRY
(2023)
Article
Cell Biology
Alexander Ries, Astrid Slany, Christine Pirker, Johanna C. C. Mader, Doris Mejri, Thomas Mohr, Karin Schelch, Daniela Flehberger, Nadine Maach, Muhammad Hashim, Mir Alireza Hoda, Balazs Dome, Georg Krupitza, Walter Berger, Christopher Gerner, Klaus Holzmann, Michael Grusch
Summary: In this study, novel hTERT-transduced mesothelial cell and Meso-CAF models were generated and characterized, and their impact on PM cell growth was investigated.
Article
Biochemistry & Molecular Biology
Martin Schaier, Enrico Falcone, Tomas Prstek, Bertrand Vileno, Sonja Hager, Bernhard K. Keppler, Petra Heffeter, Gunda Koellensperger, Peter Faller, Christian R. Kowol
Summary: Thiosemicarbazones (TSCs) are biologically active compounds that have potential anticancer activity by chelating iron and targeting ribonucleotide reductase. Recent findings suggest that the stability and reduction properties of copper complexes are essential for the action of specific TSC derivatives. This study investigated the interaction between TSCs and human serum albumin (HSA) as a potential source of copper, and found that TSCs specifically chelate copper from HSA and form ternary HSA conjugates.
Article
Chemistry, Inorganic & Nuclear
Alexander Kastner, Theresa Mendrina, Florian Bachmann, Walter Berger, Bernhard K. Keppler, Petra Heffeter, Christian R. Kowol
Summary: In this study, oxaliplatin(iv)-based complexes were developed as platinum(iv) prodrugs to release aspirin, which has shown antitumor activity against colon cancer. The newly synthesized complex demonstrated increased reduction stability compared to a cisplatin analog and exhibited desired prodrug properties in cell culture. A derivative with albumin-binding properties showed improved pharmacokinetics and tumor accumulation, leading to enhanced antitumor activity and overall survival in tumor-bearing mice.
INORGANIC CHEMISTRY FRONTIERS
(2023)
