Article
Chemistry, Multidisciplinary
Qingfeng Li, Victoria A. Maola, Nicholas Chim, Javeena Hussain, Adriana Lozoya-Colinas, John C. Chaput
Summary: This study expands the chemical space of evolvable nucleic acid systems by introducing diverse functional groups at the C-5 position of alpha-L-threofuranosyl uridine nucleoside triphosphate (tUTP), providing a synthetic route to therapeutic aptamers with high biological stability. Structural insights into TNA synthesis were obtained from a high-resolution X-ray crystal structure analysis, revealing a large cavity in the enzyme active site that accommodates the modification of tUTP substrates. The findings offer a promising route to artificially modified genetic polymers uniformly enhanced with diversity-enhancing functional groups.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Yuqin Wang, Pingping Fan, Shanyu Zhang, Liying Wang, Xinyue Li, Wendong Jia, Yao Liu, Kefan Wang, Xiaoyu Du, Panke Zhang, Shuo Huang
Summary: In this study, a specially engineered nanopore sensor was used to successfully discriminate all canonical ribonucleoside mono-, di-, and triphosphates, and a machine-learning algorithm was developed with a general accuracy of 99.9% for ribonucleotide sensing. This sensing strategy was also applied to identify ribonucleotide components in different phosphorylated forms.
Article
Chemistry, Multidisciplinary
Xiao Jia, Dominique Schols, Chris Meier
Summary: This article describes the synthesis of two types of nucleotide prodrugs containing different nucleoside analogs and their effective inhibition against HIV-2 replication. The prodrugs exhibited high stability and antiviral activity in cell extracts.
Article
Biochemistry & Molecular Biology
Chiara Figazzolo, Frederic Bonhomme, Saidbakhrom Saidjalolov, Melanie Etheve-Quelquejeu, Marcel Hollenstein
Summary: The emergence of drug-resistant strains has led to the failure of many potent antibiotics in treating bacterial infections. This article presents a novel approach of using nucleotides connected to antibiotics to identify aptamers that can restore the bactericidal activities of drugs. The authors report the synthesis of a modified nucleoside triphosphate and demonstrate its compatibility with SELEX methodology, opening up possibilities for identifying vancomycin-modified aptamers.
Article
Chemistry, Analytical
David Kodr, Mayreli Ortiz, Veronika Sykorova, Cansu Pinar Yenice, Zbigniew J. Lesnikowski, Ciara K. O'Sullivan, Michal Hocek
Summary: The previous approach of orthogonal multipotential redox coding only allowed analysis of relative nucleotide composition of short DNA stretches. In this study, two methods for normalization of electrochemical readout were presented, enabling determination of total nucleotide composition. The first method involved the presence or absence of an internal standard in the DNA primer, while the second method utilized a viologen-modified primer acting as a reference label for signal normalization. Both methods accurately analyzed DNA sequences and demonstrated potential for targeted DNA sequence analysis.
ANALYTICAL CHEMISTRY
(2023)
Article
Polymer Science
Haoying Wang, Fangyu Wang, Pengpeng Deng, Jinping Zhou
Summary: Functional polymer based on renewable material MC was modified with TPE to form a fluorescent derivative with thermoresponsive and biocompatible properties, suitable for bioimaging applications.
MACROMOLECULAR RAPID COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
David Kodr, Erika Kuzmova, Radek Pohl, Tomas Kraus, Michal Hocek
Summary: We designed and synthesized lipid-modified dNTPs, which served as substrates for DNA polymerase and could be incorporated simultaneously into the DNA strand. These lipid-ON probes showed enhanced membrane anchoring efficiency and better stability in the cell membrane compared to commonly studied ON analogues. The probes were detected at the cell surface even after 24 hours, indicating their long-lasting effect.
Article
Chemistry, Multidisciplinary
Jacob M. Sawyer, Kellan T. Passow, Daniel A. Harki
Summary: Fluorescent nucleosides are important chemical tools in biochemical research and are widely used in nucleic acids for various applications. The commonly used 2-aminopurine-2'-deoxyribonucleoside (2APN) has limitations in terms of Stokes shift, molar extinction coefficient, and quantum yield. In this study, we introduced a new fluorescent nucleoside, 4-cyanoindole-2'-deoxyribonucleoside (4CIN), which showed improved photophysical characteristics compared to 2APN. We further synthesized analogues combining the features of 2APN and 4CIN, and evaluated their photophysical properties. Nucleosides 2-6 demonstrated diverse photophysical properties, with some outperforming 4CIN. The structure-function relationship data obtained from this study can guide the design of next-generation fluorescent indole nucleosides.
Article
Chemistry, Multidisciplinary
Hao Nian, Lin Cheng, Ling Wang, Haiyang Zhang, Pinpin Wang, Yawen Li, Liping Cao
Summary: In this study, an achiral anthracene-based tetracationic nanotube was reported to exhibit two levels of supramolecular chirality. The nanotube shows conformationally adaptive host-guest complexation with nucleoside triphosphates and twisted packing of chiral host-guest complexes in water. Interestingly, the nanotube demonstrates chiral recognition for ATP/GTP and CTP/UTP through structural transformation, leading to adaptive chirality with opposite CD responses, and promoting strong circularly polarized luminescence in water.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Cell Biology
Elena J. Ciesielska, Shalom Kim, Hyacintha-Ghislaine M. Bisimwa, Cody Grier, Md Mostafijur Rahman, Carolyn K. J. Young, Matthew J. Young, Marcos T. Oliveira, Grzegorz L. Ciesielski
Summary: The study showed that the active metabolite of remdesivir, RTP, can impede the synthetic activity of the replicative mitochondrial DNA polymerase Pol gamma. However, there was no evidence of deleterious effects on the mitochondrial genome integrity in human cells treated with remdesivir.
Article
Chemistry, Organic
Ying-Ying Dong, Hua-Shan Huang, Ren-Yuan Zhong, Shan-Shan Gong, Qi Sun
Summary: α-P-modified nucleoside triphosphates (NTP alpha Xs), an important class of nucleoside triphosphate analogues, have been recognized as versatile tools in molecular biology and medicinal chemistry. However, the available synthetic methods for NTP alpha Xs are only low to moderate-yielding. In this study, we developed a new method based on linear (PPPIII)-P-V-P-V-nucleoside intermediates to access NTP alpha Xs.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Applied
Hui Xu, Guohua Shen, Cheng Peng, Xiumin Han, Liping Duan, Tanyu Cheng
Summary: A new fluorescence probe BDY-OH was developed for efficient detection of HSA, showing high signal to noise ratio and selectivity, and exhibited excellent recognition rate in clinical urine samples, suggesting great potential for early diagnosis of kidney related diseases.
Article
Chemistry, Applied
Sumei Ren, Mark A. Huffman, Aaron M. Whittaker, Hao Yang, Christopher C. Nawrat, David J. Waterhouse, Kevin M. Maloney, Neil A. Strotman
Summary: The synthesis of the carbon-14-labeled unnatural nucleoside islatravir, an investigational HIV drug, was achieved through a one-pot biocatalytic cascade starting from acetaldehyde-2-C-14. Combining enzymatic reactions into multistep biocatalytic cascades not only accelerates delivery and increases the yield, but also eliminates handling of radioactive intermediates and minimizes radioactive waste.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2021)
Article
Chemistry, Analytical
Xinran Dong, Yuchen Huang, Dechen Jiang
Summary: A fluorescent polymerase chain reaction (PCR) nanokit was established for detecting specific DNA sequences in single living cells. This strategy involves sorting the DNA sequence in a cellular nucleus into a nanopipette, where it reacts with PCR kit components to complete a PCR amplification reaction. The presence of the target DNA sequence is validated through an increase in fluorescence, and the nanokit offers a general and highly sensitive approach for single cell analysis.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Celeste Felion, Ricardo Lopez-Gonzalez, Alan L. Sewell, Rodolfo Marquez, Caroline Gauchotte-Lindsay
Summary: In this study, fluorescently labeled estrogens were developed as surrogates for studying biodegradation in environmental bacteria. The developed analytical methods allow for concurrent analysis of both fluorescent and natural estrogens. It was found that BODIPY-labeled estrogens are viable substitutes for investigating biodegradation processes.
Article
Chemistry, Multidisciplinary
Maria Brunderova, Matous Kromer, Marta Vlkova, Michal Hocek
Summary: We designed and synthesized a chloroacetamide-linked 7-deaza-ATP substrate for T7 RNA polymerase, which was used to synthesize reactive RNA probes with one or more reactive modifications. The modified RNA probes reacted with thiol-containing molecules and cysteine- or histidine-containing peptides, forming stable covalent products. They also selectively reacted with RNA-binding proteins, forming cross-linked conjugates with high conversions due to proximity effect. Our modified nucleotide and RNA probes are promising tools for RNA (bio)conjugations or RNA proteomics applications.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemical Research Methods
Miroslav Kuba, Radek Pohl, Tomas Kraus, Michal Hocek
Summary: Nucleosides and 2'-deoxyribonucleoside triphosphates (dNTPs) containing a bodipy fluorophore attached to position S of 2'-deoxycytidine were synthesized. They exhibited strong fluorescence and sensitivity to viscosity. The modified dNTPs served as substrates for DNA polymerases and were used for enzymatic synthesis of labeled DNA. The modified DNA probes acted as viscosity sensors, responding to protein binding. The dNTP with a longer linker was successfully transported into live cells and incorporated into genomic DNA, enabling DNA staining and imaging of DNA synthesis.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Vaclav Houska, Egor Ukraintsev, Jaroslav Vacek, Jiri Rybacek, Lucie Bednarova, Radek Pohl, Irena G. Stara, Bohuslav Rezek, Ivo Stary
Summary: The synthesis of helically chiral macrocycles composed of dibenzo[5]helicene units and trans-stilbene-4,4'-diyl linkers is reported. Different stereoisomers of these macrocycles were obtained through chiral resolution. The self-assembly of these macrocycles into long 1D molecular stripes in ordered 2D nanocrystals was studied using AFM.
Article
Biochemical Research Methods
Ambra Spampinato, Erika Kuzmova, Radek Pohl, Veronika Sykorova, Milan Vrabel, Tomas Kraus, Michal Hocek
Summary: A series of modified dNTPs with different linkers were designed and synthesized as substrates for DNA polymerase. The reactivity of these modified nucleotides and DNA was systematically tested and compared in click reactions. The longer linker was found to be crucial for efficient labeling. These modified dNTPs were transported into live cells and successfully used for staining DNA and imaging DNA synthesis within short time periods. This method provides a new approach for in cellulo metabolic labeling and imaging of DNA synthesis that overcomes previous limitations.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Catherine Mulholland, Ivana Jestrabova, Arghya Sett, Marek Ondrus, Veronika Sykorova, C. Lorena Manzanares, Oliver Simoncik, Petr Muller, Michal Hocek
Summary: The authors describe the selection of hydrophobic 7-phenylbutyl-7-deazaadenine-modified DNA aptamers against Heat Shock Protein 70 using PEX and magnetic bead-based SELEX. The modified aptamers showed higher binding affinity to Hsp70 than their natural counterparts and have potential for diagnostic or therapeutic applications.
COMMUNICATIONS CHEMISTRY
(2023)
Article
Chemistry, Analytical
David Kodr, Mayreli Ortiz, Veronika Sykorova, Cansu Pinar Yenice, Zbigniew J. Lesnikowski, Ciara K. O'Sullivan, Michal Hocek
Summary: The previous approach of orthogonal multipotential redox coding only allowed analysis of relative nucleotide composition of short DNA stretches. In this study, two methods for normalization of electrochemical readout were presented, enabling determination of total nucleotide composition. The first method involved the presence or absence of an internal standard in the DNA primer, while the second method utilized a viologen-modified primer acting as a reference label for signal normalization. Both methods accurately analyzed DNA sequences and demonstrated potential for targeted DNA sequence analysis.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Miroslav Kuba, Petro Khoroshyy, Martin Lepsik, Erika Kuzmova, David Kodr, Tomas Kraus, Michal Hocek
Summary: A modified dC(TO)TP was designed and synthesized with a thiazole orange moiety tethered via an oligoethylene glycol linker. It could be incorporated into DNA by DNA polymerases in vitro and live cells. The fluorescence lifetime of the thiazole orange moiety differed significantly when dC(TO)TP was incorporated into DNA compared to its non-incorporated forms. By delivering dC(TO)TP into live U-2 OS cells using a synthetic nucleoside triphosphate transporter, it enabled real-time detection and monitoring of cells actively synthesizing DNA from the beginning.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Chao Yang, Michal Tichy, Lenka Postova Slavetinska, Enzo Vaiedelich, Sona Gurska, Petr Dzubak, Marian Hajduch, Michal Hocek
Summary: This study reports the design and synthesis of a series of benzofuro-fused 7-deazapurine nucleosides and ribonucleosides. The target compounds were successfully synthesized through multiple reactions, and showed moderate to weak cytostatic activity and interesting fluorescence properties.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Natalia Kuprikova, Marek Ondrus, Lucie Bednarova, Miguel Riopedre-Fernandez, Lenka Postova Slavetinska, Veronika Sykorova, Michal Hocek
Summary: Researchers designed and synthesized a set of new DNA nucleotide derivatives, which were successfully used for DNA modification and hypermodification. The study found that one to two modified nucleotides could achieve exponential amplification in PCR, while three to four modified nucleotides only achieved linear amplification. In addition, hypermodified DNA exhibited a different secondary structure.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Mayreli Ortiz, Miriam Jauset-Rubio, Olivia Trummer, Ines Foessl, David Kodr, Josep Lluis Acero, Mary Luz Botero, Phil Biggs, Daniel Lenartowicz, Katerina Trajanoska, Fernando Rivadeneira, Michal Hocek, Barbara Obermayer-Pietsch, Ciara K. O'Sullivan
Summary: A generic platform was developed for cost-effective and rapid electrochemical SNP genotyping from fingerprick blood samples, enabling early diagnosis of osteoporosis. The platform utilizes isothermal solid-phase primer elongation with ferrocene-labeled nucleoside triphosphates, allowing for targeted genotyping of SNPs associated with osteoporosis. The system was validated using real blood samples, with results matching those from Taqman SNP genotyping assays and Sanger sequencing. The platform is highly versatile and has the potential to be deployed in an automated device for targeted SNP genotyping.
ACS CENTRAL SCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Ivana Jestrabova, Lenka Postova Slavetinska, Michal Hocek
Summary: We designed and synthesized a series of novel nucleoside phosphoramidites for the solid-phase synthesis of modified oligonucleotides. The hybridization properties of these modified oligonucleotides were studied, and they have potential for the synthesis of highly modified functional nucleic acid-based polymers.
Article
Chemistry, Multidisciplinary
Vladimir Motornov, Radek Pohl, Blanka Klepetarova, Petr Beier
Summary: Elusive N-acyl-1,2,3-triazoles formed by direct acylation of NH-1,2,3-triazoles were isolated and characterized. Thermodynamic N2 isomers were found to be preferred. Direct evidence of interconversion between N1- and N2-acyltriazoles confirmed their usefulness in denitrogenative transformations. An efficient synthesis of enamido triflates from NH-triazoles via N2-acyl-1,2,3-triazole intermediates was developed.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
David Kodr, Erika Kuzmova, Radek Pohl, Tomas Kraus, Michal Hocek
Summary: We designed and synthesized lipid-modified dNTPs, which served as substrates for DNA polymerase and could be incorporated simultaneously into the DNA strand. These lipid-ON probes showed enhanced membrane anchoring efficiency and better stability in the cell membrane compared to commonly studied ON analogues. The probes were detected at the cell surface even after 24 hours, indicating their long-lasting effect.
Article
Chemistry, Multidisciplinary
Anna Kovalova, Vit Prouza, Martin Zavrel, Miroslav Hajek, Rastislav Dzijak, Alzbeta Magdolenova, Radek Pohl, Zdenek Voburka, Kamil Parkan, Milan Vrabel
Summary: This study presents a method for identifying lectin-binding ligands with low micromolar affinity by screening synthetic click glycopeptide libraries. The selected glycopeptides showed enhanced binding potency to the target lectins compared to the starting sugar moieties. This approach offers a promising alternative means of discovering ligands for galectins and other carbohydrate-binding proteins.
Review
Biology
Walter Wolfsberger, Karishma Chhugani, Khrystyna Shchubelka, Alina Frolova, Yuriy Salyha, Oksana Zlenko, Mykhailo Arych, Dmytro Dziuba, Andrii Parkhomenko, Volodymyr Smolanka, Zeynep H. Guemues, Efe Sezgin, Alondra Diaz-Lameiro, Viktor R. Toth, Megi Maci, Eric Bortz, Fyodor Kondrashov, Patricia M. Morton, Pawel P. Labaj, Veronika Romero, Jakub Hlavka, Serghei Mangul, Taras K. Oleksyk
Summary: Conflicts and natural disasters not only cause destruction to lives, but also have a significant negative impact on the scientific advancements of the affected countries. These events result in infrastructure collapse, destruction of educational and research institutions, and hinder the progress of scientists. In our interconnected world, conflicts and disasters have far-reaching effects on the global community.
