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, 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, 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.
Review
Chemistry, Multidisciplinary
Marta Rachwalak, Joanna Romanowska, Michal Sobkowski, Jacek Stawinski
Summary: This review briefly explains the chemical synthesis of nucleoside di- and triphosphates within a historical background, and discusses their potential use as pronucleotides in anti-HIV therapy.
APPLIED SCIENCES-BASEL
(2021)
Article
Chemistry, Medicinal
Karolina Vankova, Eva Dolezelova, Eva Tloustova, Dana Hockova, Alena Zikova, Zlatko Janeba
Summary: A series of novel 7-aryl-7-deazaadenine-based N-branched acyclic nucleoside phosphonates (aza-ANPs) were synthesized using the optimized Suzuki cross-coupling reaction. Compound 14h, which contains two phosphonate moieties, showed potent anti-trypanosomal activity and low micromolar cytotoxicity against leukemia and/or cancer cell lines.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
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
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
Biochemistry & Molecular Biology
Dmitry A. Tatarinov, Bulat F. Garifullin, Mayya G. Belenok, Olga Andreeva, Irina Yu Strobykina, Anna Shepelina, Vladimir V. Zarubaev, Alexander Slita, Alexandrina S. Volobueva, Liliya F. Saifina, Marina M. Shulaeva, Vyacheslav E. Semenov, Vladimir E. Kataev
Summary: A series of nucleoside analogues containing 1,2,3-triazole moiety attached to uracil or quinazoline-2,4-dione were synthesized and evaluated for their antiviral activity against influenza virus. Three compounds showed moderate activity, while the remaining compounds were inactive. Molecular docking simulations supported the mechanism of antiviral action of these analogues.
Article
Chemistry, Multidisciplinary
David Kodr, Cansu Pinar Yenice, Anna Simonova, Dijana Pavlovic Saftic, Radek Pohl, Veronika Sykorova, Mayreli Ortiz, Ludek Havran, Miroslav Fojta, Zbigniew J. Lesnikowski, Ciara K. O'Sullivan, Michal Hocek
Summary: A series of modified nucleoside triphosphates bearing dicarba-nido-undecaborate or metal bis(dicarbollide) groups were prepared and utilized for DNA synthesis and redox labeling. The combination of these redox labels allowed for the first fully orthogonal redox coding of all four canonical nucleobases, enabling determination of nucleobase composition of short DNA stretches with electrochemical readout in one simple primer extension experiment.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Svetlana V. Vasilyeva, Alexandra A. Kuznetsova, Elizaveta E. Baranovskaya, Nikita A. Kuznetsov, Alexander A. Lomzov, Dmitrii V. Pyshnyi
Summary: Efficient protocols were developed for the synthesis of a new compound - nucleoside 5'-alpha-iminophosphates using the Staudinger reaction. The synthesized ppp(DMI)T showed good hydrolytic stability and can serve as a substrate for template-independent DNA synthesis catalyzed by TdT.
BIOORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Katarzyna Jastrzebska, Anna Maciaszek, Rafal Dolot, Agnieszka Tomaszewska-Antczak, Barbara Mikolajczyk, Piotr Guga
Summary: This study synthesized and investigated Oxathiaphospholane derivatives of ribonucleosides, and demonstrated that their specific configurations have no correlation with the thermal stability of DNA and RNA duplexes.
Article
Biochemical Research Methods
Emma K. Davison, David A. Petrone, Michael Meanwell, Matthew B. Nodwell, Steven M. Silverman, Louis-Charles Campeau, Robert Britton
Summary: This protocol presents a novel method for the synthesis of nucleoside analogs, addressing several challenges and allowing for flexible and selective access to these valuable compounds from simple starting materials.
Article
Chemistry, Organic
Raphael Bereiter, Marco Oberlechner, Ronald Micura
Summary: Imidazopyridines and pyrrolopyrimidines are important compounds in medicinal chemistry, especially in the context of RNA atomic mutagenesis. The demand for 1-deazaguanine (c1G base) has increased, but synthetic access is challenging. This study presents a new six-step synthesis for c1G base starting from 6-iodo-1-deazapurine, involving copper-catalyzed C-O bond formation and site-specific nitration. The route also allows for the synthesis of 1-deazahypoxanthine (c1I base).
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Physical
Martyna Koplunaite, Kamile Butkute, Dominykas Spelveris, Nina Urbeliene, Rolandas Meskys
Summary: There are various applications for nucleosides, nucleotides, and their analogues, including enzymatic research and drug development. This study compares the performance of two nucleoside kinases in nucleotide phosphorylation reactions and finds that deoxynucleoside kinase shows better substrate range and reaction yields.
