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.
Review
Biochemistry & Molecular Biology
Patricia M. Toro, Marianela Saldias, Gabriela Valenzuela-Barra
Summary: This study provides a comprehensive review of metal compound G4 binders and their structural features that enable them to recognize G-quartets and stabilize DNA G4 structures.
CURRENT MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Loukiani Savva, Savvas N. Georgiades
Summary: G-quadruplexes, a family of tetraplex helical nucleic acid topologies, have shown potential for anticancer research due to their presence in functionally-important regions of the human genome and their ability to exert anticancer effects. Despite only a few lead compounds progressing to clinical trials, recent advancements in the field have created conditions for further development of drug candidates targeting G-quadruplexes.
Article
Materials Science, Biomaterials
Paulina Chytrosz-Wrobel, Monika Golda-Cepa, Kamil Drozdz, Jakub Rysz, Piotr Kubisiak, Waldemar Kulig, Monika Brzychczy-Wloch, Lukasz Cwiklik, Andrzej Kotarba
Summary: This study investigates the effect of oxygen plasma treatment on the physicochemical properties of polyurethane surfaces and characterizes the polyurethane-water interfaces in detail through experiments and molecular dynamics simulations.
ACS BIOMATERIALS SCIENCE & ENGINEERING
(2023)
Article
Plant Sciences
Jia-Hong Lin, Ming-Hao Hu
Summary: This study demonstrates that the alkaloid Lycobetaine (LYC) preferentially binds to c-MYC and BCL-2 promoter G-quadruplexes (G4s) and stabilizes them through end-stacking mode. LYC inhibits the expression of c-MYC and BCL-2 oncogenes, leading to cell cycle arrest, apoptosis, as well as inhibition of cell proliferation and migration. These results reveal a new potential anticancer mechanism and application of LYC in drug-resistant cancers.
PHYTOCHEMISTRY LETTERS
(2022)
Article
Biochemical Research Methods
Mohammed Enamul Hoque, Golam Mustafa, Soumitra Basu, Hamza Balci
Summary: Using dCas9, transcription levels of TH can be modulated by targeting different parts of a G-rich sequence within the promoter. The presence of GQs in target sequences impacts DNA cleavage activity of Cas9, with a significant reduction in cleavage activity when targeting high-stability GQs. Additionally, this reduction is more pronounced for the G-rich strand compared to the complementary C-rich strand.
ACS SYNTHETIC BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Carla Bazzicalupi, Alessandro Bonardi, Tarita Biver, Marta Ferraroni, Francesco Papi, Matteo Savastano, Paolo Lombardi, Paola Gratteri
Summary: The interaction between a series of berberine derivatives and human telomeric G-quadruplexes was investigated in this study. The results showed the formation of 1:1 complexes between the derivatives and Tel12. The linkers' length had a correlation with the strength of binding and affected the G4 stabilization effect. This study provides important insights into the mechanism of berberine derivatives in inhibiting telomerase activity in malignant cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Riccardo Rigo, Elisabetta Groaz, Claudia Sissi
Summary: In the study of designing small molecules to target specific genomic sites controlling gene expression, G-quadruplexes at oncogene promoters have been considered as ideal targets. However, the lack of correlation between G-quadruplex targeting and protein expression hampers pharmaceutical applications. The wide genomic localization and polymorphic behavior of G-quadruplexes may account for this, calling for more focused drug design strategies.
Article
Chemistry, Physical
Ronan Bellabarba, Peter Johnston, Steven Moss, Carsten Sievers, Bala Subramaniam, Cathy Tway, Ziyuan Wang, Hongda Zhu
Summary: This Viewpoint discusses the implications of the net zero energy transition on traditional chemical feedstocks and catalytic elements. Some trends from scenarios already underway suggest that electric passenger vehicles will reduce petroleum refining output, creating supply gaps and changing dynamics for critical metals. However, emerging feedstocks such as biomass and recycled carbon could bridge the gaps, while displaced catalytic metals may be available for chemicals and aviation fuels from these feedstocks. The availability of carbon-free hydrogen and oxygen can contribute to decarbonization of the chemical industry.
Article
Chemistry, Physical
Pallavi Agrawal, Maya S. Nair
Summary: This study evaluated the binding of andrographolide with CREB1 G-quadruplex and Thrombin Binding Aptamer (TBA) using molecular docking, dynamics, and simulation. The data showed that andrographolide can stabilize G-quadruplexes. It binds to the CREB1 G-quadruplex by forming hydrogen bonds and has the potential to target G-quadruplex forming DNA sequences in various oncogenes.
MOLECULAR SIMULATION
(2023)
Article
Virology
Yance Zhu, Wenhao Liu, Chao Zhang
Summary: This study identified two novel G4-forming sequences, OriL-A and OriL-S, in the PRV genome, which can fold into parallel G4 structures in vitro. Treatment of PRV-infected cells with the G4 stabilizer PhenDC3 significantly inhibited PRV DNA replication in host cells, without affecting PRV attachment and entry. These findings suggest that G4 may serve as an innovative therapeutic target against PRV.
Article
Multidisciplinary Sciences
Claire L. Price, Andrew G. S. Warrilow, Nicola J. Rolley, Josie E. Parker, Vera Thoss, Diane E. Kelly, Nicolae Corcionivoschi, Steven L. Kelly
Summary: The cytochrome P450 CYP168A1 from Pseudomonas aeruginosa was cloned and expressed in Escherichia coli. It was found that CYP168A1 is a fatty acid hydroxylase that hydroxylates saturated fatty acids at both the omega-1- and omega-2-positions, and unsaturated fatty acids at the omega-1-position. The study also showed that CYP168A1 has a preference for palmitic, oleic, and stearic acids as substrates, which is consistent with the phosphatidylcholine-rich environment in the lung colonized by P. aeruginosa.
Article
History & Philosophy Of Science
Isabel Pont Niclos, Jorge Gonzalez Garcia
Summary: This article introduces the double helix structure of DNA and other structures such as G-quadruplexes. It discusses the cellular functions of G-quadruplexes, particularly their potential as molecular targets for cancer therapies.
METODE SCIENCE STUDIES JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Thomas A. Wieser, Deborah S. Wuttke
Summary: RPA forms a dynamic complex with ssDNA and engages with DNA in different modes, which is important for maintaining genome integrity. Different binding modes have different effects on RPA's interaction with biologically relevant ligands, and the core DNA-binding domains play a crucial role in these interactions.
Article
Multidisciplinary Sciences
Juan Sebastian Reyes, Eduardo Fuentes-Lemus, Juan David Figueroa, Javier Rojas, Angelica Fierro, Felipe Arenas, Per M. Hagglund, Michael J. Davies, Camilo Lopez-Alarcon
Summary: Escherichia coli glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) were studied for their susceptibility to oxidation by peroxyl radicals (ROO) and mechanisms of inactivation. Results showed that G6PDH underwent dispersed modifications distant from its active site, predominantly targeting Trp and Met residues, while 6PGDH experienced more localized oxidation near its catalytic site, leading to high susceptibility to inactivation by ROO.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Ramsay J. McFarlane, Julia Feichtinger, Lee Larcombe
Letter
Endocrinology & Metabolism
Ralf J. M. Weber, Catherine L. Winder, Lee D. Larcombe, Warwick B. Dunn, Mark R. Viant
Article
Biochemical Research Methods
Bastian Schiffthaler, Myrto Kostadima, Nicolas Delhomme, Gabriella Rustici
PLOS COMPUTATIONAL BIOLOGY
(2016)
Article
Urology & Nephrology
Marta Mateus, Marcus M. Ilg, William J. Stebbeds, Nim Christopher, Asif Muneer, David J. Ralph, Selim Cellek
JOURNAL OF SEXUAL MEDICINE
(2018)
Editorial Material
Andrology
Selim Cellek, William Stebbeds, David J. Ralph
ASIAN JOURNAL OF ANDROLOGY
(2014)
Editorial Material
Cell Biology
Ramsay J. McFarlane, Julia Feichtinger, Lee Larcombe
Article
Oncology
Julia Feichtinger, Lee Larcombe, Ramsay J. McFarlane
INTERNATIONAL JOURNAL OF CANCER
(2014)
Article
Mathematical & Computational Biology
Julia Feichtinger, Ramsay J. McFarlane, Lee D. Larcombe
DATABASE-THE JOURNAL OF BIOLOGICAL DATABASES AND CURATION
(2014)
Article
Microbiology
Bhupesh K. Prusty, Nitish Gulve, Sheila Govind, Gerhard R. F. Krueger, Julia Feichtinger, Lee Larcombe, Richard Aspinall, Dharam Ablashi, Carla T. Toro
FRONTIERS IN MICROBIOLOGY
(2018)
Article
Urology & Nephrology
Marcus M. Ilg, Marta Mateus, William J. Stebbeds, Uros Milenkovic, Nim Christopher, Asif Muneer, Maarten Albersen, David J. Ralph, Selim Cellek
Article
Biochemical Research Methods
Kim T. Gurwitz, Prakash Singh Gaur, Louisa J. Bellis, Lee Larcombe, Eva Alloza, Balint Laszlo Balint, Alexander Botzki, Jure Dimec, Victoria Dominguez del Angel, Pedro L. Fernandes, Eija Korpelainen, Roland Krause, Mateusz Kuzak, Loredana Le Pera, Brane Leskosek, Jessica M. Lindvall, Diana Marek, Paula A. Martinez, Tuur Muyldermans, Stale Nygard, Patricia M. Palagi, Hedi Peterson, Fotis Psomopoulos, Vojtech Spiwok, Celia W. G. van Gelder, Allegra Via, Marko Vidak, Daniel Wibberg, Sarah L. Morgan, Gabriella Rustici
PLOS COMPUTATIONAL BIOLOGY
(2020)
Review
Biology
Roberta Bergero, Peter Ellis, Wilfried Haerty, Lee Larcombe, Iain Macaulay, Tarang Mehta, Mette Mogensen, David Murray, Will Nash, Matthew J. Neale, Rebecca O'Connor, Christian Ottolini, Ned Peel, Luke Ramsey, Ben Skinner, Alexander Suh, Michael Summers, Yu Sun, Alison Tidy, Raheleh Rahbari, Claudia Rathje, Simone Immler
Summary: The separation of germ cell populations from the soma plays a crucial role in genetic inheritance and evolutionary transition to multicellularity. Molecular processes affecting the germline genome, such as segregation, recombination, mutation, and selection, can alter allele frequencies and potentially deviate from Mendelian inheritance. The use of new sequencing technologies has opened up opportunities to delve into the micro-evolutionary processes occurring at the germline genome level.
BIOLOGICAL REVIEWS
(2021)
Article
Cell & Tissue Engineering
Hongbin Yang, Will Stebbeds, Jo Francis, Amy Pointon, Olga Obrezanova, Kylie A. Beattie, Peter Clements, James S. Harvey, Graham F. Smith, Andreas Bender
Summary: This study derived, evaluated, and applied 38 waveform parameters using a novel Python framework and trained a machine learning model to predict cardiac activity. The results demonstrate that machine learning can reduce user-to-user variability and bias in assessing cardiovascular risk from waveform data.
Article
Pharmacology & Pharmacy
Hongbin Yang, Olga Obrezanova, Amy Pointon, Will Stebbeds, Jo Francis, Kylie A. Beattie, Peter Clements, James S. Harvey, Graham F. Smith, Andreas Bender
Summary: Functional changes to cardiomyocytes during drug discovery pose risks of cardiovascular adverse effects. A new approach using calcium transients in hiPSC-CMs has been developed to detect early contractility changes. By deriving 25 parameters from each calcium transient waveform, a modified Random Forest method was able to predict inotropic effects with improved accuracy compared to traditional methods. This study demonstrates the potential of advanced waveform parameters and machine learning techniques in predicting cardiovascular risks associated with inotropic effects.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2023)
Article
Toxicology
William Stebbeds, Kavita Raniga, David Standing, Iona Wallace, James Bayliss, Andrew Brown, Richard Kasprowicz, Deidre Dalmas Wilk, Julianna Deakyne, Peter Clements, Khuram W. Chaudhary, Eric Rossman, Anthony Bahinski, Jo Francis
Summary: Cardiovascular toxicity is a major cause of drug failures and withdrawals in drug development. Current methods for early assessment of cardiovascular liabilities only capture acute functional cardiotoxicity but fail to detect structural cardiotoxicity that occurs after chronic exposure. CardioMotion is a novel label-free assay that records and assesses the beating of cardiomyocytes and can identify compounds that impact beating, providing a promising tool for early safety assessment.
TOXICOLOGICAL SCIENCES
(2023)