Article
Biochemistry & Molecular Biology
Peng Gong
Summary: This study focuses on viral RdRP NAC and related mechanisms that have not been structurally clarified, discussing potential factors such as movement along the template strand, cleavage of the product strand, and the impact of non-cognate NTP substrates on the NAC process, emphasizing the complications and challenges that may arise in these areas.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Chemistry, Analytical
Elena Suprun, Svetlana A. Khmeleva, Konstantin Bibik, Konstantin G. Ptitsyn, Leonid K. Kurbatov, Sergey P. Radko
Summary: In this study, modified dUTP-Fl and dUTP-Rh were used as substrates and electroactive labels for electrochemical detection of dsDNA amplification products. The results showed that dUTP-Fl had better compatibility with PCR and RPA, allowing the direct electrochemical detection of full-size amplicons at micromolar concentrations when substituted in the reaction mixture at 50-90% of dTTP.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2023)
Article
Biotechnology & Applied Microbiology
Ayokunle O. Olanrewaju, Benjamin P. Sullivan, Alicia H. Gim, Cosette A. Craig, Derin Sevenler, Andrew T. Bender, Paul K. Drain, Jonathan D. Posner
Summary: This study introduces a new probabilistic model, RESTRICT, and demonstrates the selective measurement of multiple nucleotide analogs using DNA templates designed according to the chemical structure of each drug. Experimental results validate the measurement of tenofovir diphosphate, emtricitabine triphosphate, lamivudine triphosphate, and azidothymidine triphosphate, showing agreement with the theoretical predictions. RESTRICT represents a novel activity-based assay for therapeutic drug monitoring in HIV care, with potential applications in other diseases treated with nucleotide analogs.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Hui Shi, Ren Ishikawa, Choon Han Heh, Shigeki Sasaki, Yosuke Taniguchi
Summary: MTH1 is an enzyme that hydrolyzes oxidatively damaged nucleobase to prevent its mis-incorporation into genomic DNA. Research on new compounds has revealed the potential of strong inhibitory effects on MTH1 activity and interactions with its active site.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Environmental Sciences
Yao Tian, Lijia Liu, Yudan Wang, Fuqiu Ma, Chunhong Zhang, Hongxing Dong
Summary: A novel porous uranium adsorbent (PA-HCP) with high efficiency was designed and synthesized. It exhibited a large specific surface area, excellent selectivity for uranium, and good recyclability. The grafted polyethyleneimine improved the dispersion of the adsorbents in water and facilitated uranium sorption. Overall, PA-HCP can be used as an efficient and economical sorbent for removing U(VI) from wastewater.
ENVIRONMENTAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Fumitaka Hashiya, Hirotaka Murase, Akash Chandela, Haruka Hiraoka, Masahito Inagaki, Yuko Nakashima, Naoko Abe, Mayu Nakamura, Goro Terai, Yasuaki Kimura, Kaori Ando, Natsuhisa Oka, Kiyoshi Asai, Hiroshi Abe
Summary: Controlling PCR fidelity is crucial in molecular biology, and high-fidelity PCR is essential for gene cloning. While most studies focus on protein engineering of polymerases for fidelity control, this report explores the use of chemically modified nucleotide substrates. The modification on P-gamma of nucleotide substrates was found to affect PCR fidelity, with deoxyadenosine tetraphosphate enhancing one mutation type and deoxyguanosine tetraphosphate suppressing another. By using excess amounts of deoxyguanosine tetraphosphate, both mutations were successfully suppressed, leading to improved overall fidelity.
Article
Materials Science, Textiles
Ying Liu, Li Zhou, Fang Ding, Shanshan Li, Rong Li, Zhiguang Li, Dan Huang, Xuehong Ren
Summary: A novel flame-retardant containing phosphorus and nitrogen was successfully synthesized and grafted onto cotton fabrics in this study, leading to efficient flame retardancy as confirmed by various tests. Both electron beam-cotton and pad dry cure-cotton showed good flame retardant properties, with the former exhibiting lower tensile loss and higher thermal degradation temperature compared to the latter.
JOURNAL OF INDUSTRIAL TEXTILES
(2021)
Review
Chemistry, Multidisciplinary
Junbiao Chang
Summary: Modified nucleosides have therapeutic potential in antiviral treatments, but face new challenges in the era of the COVID-19 pandemic. 4'-Modified nucleosides are an important subclass that can enhance antiviral activity and safety. Several 4'-modified nucleoside drug candidates have progressed into clinical stages, with FNC showing promise in treating HIV-1 and COVID-19.
ACCOUNTS OF CHEMICAL RESEARCH
(2022)
Article
Astronomy & Astrophysics
Zehua Tian, Jiangfeng Du
Summary: The proposed experimentally viable scheme involves using an impurity atom in a dipolar Bose-Einstein condensate to probe analogue low-energy Lorentz violation. The density fluctuations in the condensate show a Lorentz-violating Bogoliubov spectrum at high energies, with recovery of approximate Lorentz invariance at lower energy scales. These findings suggest that the modified dispersion in the system can lead to drastic Lorentz violation experienced by the impurity, providing a test field to verify unexpected imprints of high-energy structures in quantum field theory.
Article
Pharmacology & Pharmacy
Emmie de Wit, Brandi N. Williamson, Friederike Feldmann, Kerry Goldin, Michael K. Lo, Atsushi Okumura, Jamie Lovaglio, Elaine Bunyan, Danielle P. Porter, Tomas Cihlar, Greg Saturday, Christina F. Spiropoulou, Heinz Feldmann
Summary: The study found that delayed administration of remdesivir by 3 days still had some efficacy against Nipah virus infection, but it had limited preventive effects on clinical disease.
ANTIVIRAL RESEARCH
(2023)
Article
Mathematics, Applied
Yong-Mo Hu, Wen-Tao Cheng, Chun-Yan Gui, Wen-Hui Zhang
Summary: This article examines the local approximation properties of (p, q)-Szasz-Mirakjan-Kantorovich-Stancu operators with three parameters, including estimating moments and central moments, pointwise estimates, convergence rates, and weighted approximation.
JOURNAL OF FUNCTION SPACES
(2021)
Article
Chemistry, Multidisciplinary
Bei Hu, Yitao Wang, Na Li, Shun Zhang, Guangcheng Luo, Zhen Huang
Summary: A new strategy using Se-dNTPs to enhance PCR specificity and sensitivity is reported in this study, simplifying PCR design and optimization by effectively eliminating non-specific products.
CHEMICAL COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
P. A. Kaminski
Summary: Bacteriophage genomes contain 2,6 diaminopurine, a modified nucleobase that violates Watson and Crick's base pairing rules, found in various types of bacteriophages. The biosynthetic pathway for aminoadenine containing DNA and the exclusion of adenine have been elucidated, providing evidence for the exploration of non-canonical nucleic acids in synthetic biology. This natural deviation from the genetic code exemplifies the possibilities nature presents and serves as proof of concept for the synthetic biology field.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Mohamed A. Said, Amgad Albohy, Mohamed A. Abdelrahman, Hany S. Ibarhim
Summary: In this study, researchers utilized drug databases and virtual screening analysis to identify a promising candidate drug, remdesivir, against SARS-CoV-2. They also designed analogs HA-130383 and HA-130384 based on scaffold replacement and structure-based pharmacophore. These analogs showed potential as lead compounds.
Article
Chemistry, Multidisciplinary
Andreas Englert, Julian F. Vogel, Tim Bergner, Jessica Loske, Max von Delius
Summary: A growing number of out-of-equilibrium systems have been created and investigated in chemical laboratories over the past decade. In this work, a dissipative reaction network involving the chemically fueled formation of phosphoramidates from natural ribonuceotides and phosphoramidate hydrolysis as the backward reaction is described. The Design of Experiments (DoE) tool was utilized to optimize and understand the network. Additionally, transient self-assemblies were generated using the reaction cycle, with potential relevance to origin-of-life scenarios.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Organic
Mary Anne Maverick, Marie Gaillard, Jean-Jacques Vasseur, Francoise Debart, Michael Smietana
Summary: Research on the chemical functionalization at the C-5' position of nucleosides has been relatively limited, despite its potential significant role for biological activity. A new Pd-catalyzed and Cu(I)-mediated reaction method was developed in this study to synthesize diversely modified 5'-acyl nucleosides, paving the way for the preparation of a variety of potentially bioactive compounds.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Niklas Freund, Alexander Taylor, Sebastian Arangundy-Franklin, Nithya Subramanian, Sew-Yeu Peak-Chew, Amy M. Whitaker, Bret D. Freudenthal, Mikhail Abramov, Piet Herdewijn, Philipp Holliger
Summary: In this study, a two-residue "gate" was discovered in an archaeal DNA polymerase, which enables the synthesis of 2'-modified RNA oligomers. This discovery expands the application potential of 2'-modified RNA in nucleic acid therapeutics and biotechnology.
Article
Biochemistry & Molecular Biology
Kevan Perez de Carvasal, Gerard Vergoten, Jean-Jacques Vasseur, Michael Smietana, Francois Morvan
Summary: Inspired by automated DNA synthesis, phosphodiester-linked homohexamers consisting of an electron-rich DAN donor and an electron-deficient NDI acceptor were synthesized, resulting in flexible and hydrophilic hexamers. These hexamers formed fibers and hydrogels through charge transfer donor-acceptor recognition, with the resulting structure-dependent on the nature of the complementary partner.
Article
Biochemistry & Molecular Biology
Shenghua Gao, Letian Song, Hongtao Xu, Antonios Fikatas, Merel Oeyen, Steven De Jonghe, Fabao Zhao, Lanlan Jing, Dirk Jochmans, Laura Vangeel, Yusen Cheng, Dongwei Kang, Johan Neyts, Piet Herdewijn, Dominique Schols, Peng Zhan, Xinyong Liu
Summary: DF-47 and DF-51 were identified as effective inhibitors of SARS-CoV-2/DENV polymerase through RdRp inhibition screening and in vitro antiviral study. In silico simulation revealed stable binding modes between DF-47/DF-51 and SARS-CoV-2/DENV RdRp, including chelating with Mg2+ near the polymerase active site. These polyphenols have the potential to be developed into broad-spectrum, non-nucleoside RdRp inhibitors with a new scaffold.
Article
Biochemistry & Molecular Biology
Hui Yang, Elena Eremeeva, Mikhail Abramov, Maarten Jacquemyn, Elisabetta Groaz, Dirk Daelemans, Piet Herdewijn
Summary: An enzymatic method was developed to generate partially base-modified RNA constructs, as well as fully modified RNA constructs featuring multiple modified bases. The efficiency of the fully modified RNA constructs was enhanced by using different T7 RNA polymerase variants. The study also demonstrated the successful incorporation of modified bases into PCR products and the effectiveness of the modified RNA constructs in CRISPR-Cas9 cleavage assays.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Mikael Feracci, Cecilia Eydoux, Veronique Fattorini, Lea Lo Bello, Pierre Gauffre, Barbara Selisko, Priscila Sutto-Ortiz, Ashleigh Shannon, Hongjie Xia, Pei-Yong Shi, Mathieu Noel, Francoise Debart, Jean-Jacques Vasseur, Steve Good, Kai Lin, Adel Moussa, Jean-Pierre Sommadossi, Aurelie Chazot, Karine Alvarez, Jean-Claude Guilemot, Etinne Decroly, Francois Ferron, Bruno Canard
Summary: AT-752 is a guanosine analogue prodrug that is active against dengue virus (DENV) by inhibiting RNA synthesis. It targets the RNA 2'-O-MTase and RNA-dependent RNA polymerase (RdRp) activities of NS5. The crystal structure and activities of the DENV 2 MTase domain in complex with AT-9010 show its binding to the GTP/RNA-cap binding site, resulting in the inhibition of 2'-O but not N7-methylation activity.
ANTIVIRAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Cecile Gasse, Puneet Srivastava, Guy Schepers, Joachim Jose, Marcel Hollenstein, Philippe Marliere, Piet Herdewijn
Summary: Chemical cell surface modification is an important field with great potential in tissue engineering, cell-based immunotherapy, and regenerative medicine. However, research on engineering bacterial tissues through chemical cell surface modification is lacking, especially in finding suitable molecular handles. In this study, a novel strategy using orthogonal nucleic acid-protein conjugation was developed to induce artificial bacterial aggregation. This system combines the selective and stable linkage of a protein Tag at the cell surface with the modularity and reversibility of aggregation through oligonucleotide hybridization. The immobilization of XNA via covalent, SNAP-tag-mediated interactions on cell surfaces for bacterial aggregation is reported for the first time.
Article
Chemistry, Multidisciplinary
Kevan Perez de Carvasal, Laura Nicollet, Michael Smietana, Francois Morvan
Summary: The position of DAN and NDI in DNA duplexes and hairpins significantly affects their stability. Introducing a DAN/NDI pair in the center of a DNA duplex decreases its thermal stability, but the addition of a second pair restores or increases the stability. In contrast, placing DAN:NDI pairs at the ends of a duplex always leads to strong stabilization. Furthermore, a DAN:NDI pair positioned in the loop of a hairpin induces stronger stabilization than a T4 loop.
Article
Biochemistry & Molecular Biology
Pradeep S. Pallan, Terry P. Lybrand, Eriks Rozners, Mikhail Abramov, Guy Schepers, Elena Eremeeva, Piet Herdewijn, Martin Egli
Summary: Efforts are being made to create and implement alternative genetic systems with pairing components orthogonal to natural base pairs. Another approach conserves Watson-Crick pairing but substitutes one or all of the four letters of the DNA alphabet with modified components. This study analyzes the properties of a DZA DDD structure and reveals interesting findings regarding stability, hydration, structure, and dynamics.
Article
Chemistry, Medicinal
Marcel Hausdorff, Adrien Delpal, Sarah Barelier, Laura Nicollet, Bruno Canard, Franck Touret, Agathe Colmant, Bruno Coutard, Jean-Jacques Vasseur, Etienne Decroly, Francoise Debart
Summary: The COVID-19 pandemic has raised the urgent need for new therapeutic drugs targeting the SARS-CoV-2 replication machinery. This study focuses on the development of inhibitors targeting the highly conserved protein nsp14, which is involved in viral RNA translation and immune evasion. Through structure-guided drug design, 26 novel adenosine mimetics were synthesized, one of which showed selective inhibition of nsp14 N7-MTase activity with high potency against SARS-CoV-2 replication in cell culture.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Peter Schofield, Alexander Taylor, Jerome Rihon, Cristian D. Pena Martinez, Sacha Zinn, Charles-Alexandre Mattelaer, Jennifer Jackson, Gurpreet Dhaliwal, Guy Schepers, Piet Herdewijn, Eveline Lescrinier, Daniel Christ, Philipp Holliger
Summary: Nucleic acids serve as the basis of heredity and are increasingly utilized to create novel nanostructures, devices, and drugs. Chemically modified alternatives, known as xeno nucleic acids (XNAs), have been developed to expand their chemical and functional capabilities. XNA aptamers, which can bind targets with high affinity and specificity, have not been thoroughly investigated in terms of their structure and function.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Mengmeng Wang, Kunyu Qu, Peipei Zhao, Xin Yin, Yiwei Meng, Piet Herdewijn, Chao Liu, Lixin Zhang, Xuekui Xia
Summary: Gemcitabine prodrugs with modifications on the 4-N-amino group by employing an acetylated L- or D-lysine moiety masked by different substitutions were synthesized. These prodrugs showed higher anticancer activity than gemcitabine in A549 lung cells and exhibited potent activity against BxPC-3 pancreatic cells. They also showed lower toxicity towards normal cells and improved stability in various metabolic environments. Overall, acetylated lysine conjugated gemcitabine prodrugs could be promising leads for new anticancer drugs.
RSC MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Organic
Romain Amador, Adrien Delpal, Bruno Canard, Jean-Jacques Vasseur, Etienne Decroly, Francoise Debart, Guillaume Clave, Michael Smietana
Summary: N-Acylsulfonamides, possessing unique physico-chemical properties, have attracted increasing interest in medicinal chemistry. This study demonstrates the easy and efficient synthesis of N-acylsulfonamide analogues via the sulfo-click reaction.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Organic
Megane Debiais, Alejandro Gimenez Molina, Sabine Muller, Jean-Jacques Vasseur, Ivan Barvik, Carine Baraguey, Michael Smietana
Summary: Inspired by boronic acids' ability to bind with diol-containing compounds, we successfully formed boronate ester-based macrocycles through assembly in solution, and investigated their dynamic assembly and sugar pucker conformation profile.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
