Article
Chemistry, Organic
Joanna Nowak-Karnowska, Karolina Zielinska, Jan Milecki, Bohdan Skalski
Summary: The study demonstrates a highly efficient DNA duplex interstrand photocrosslinking method using ClSdU, which forms a reversible crosslink with thymine in the target strand and converts to a stable fluorescent crosslink. The results indicate the great potential of ClSdU as a valuable DNA photo-crosslinking reagent for chemical biology applications.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Yanli Wang, Shiqing Jiang, Mingxiu Chang, Chunhong Dong
Summary: The conformational features of drugs are crucial for their biological activity. This report investigated the solid-state and solution conformations of nucleosides, showing different preferences and stability. The results highlight the importance of conformational analysis for understanding drug behavior in different environments.
NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS
(2021)
Article
Chemistry, Organic
Wen-Ze Shi, Hai Li, Gui-Cai Mu, Ji-Liang Lu, Yuan-Hong Tu, Xiang-Guo Hu
Summary: The study reports for the first time that imidate radicals can efficiently add to glycals to produce glycosyl radicals, leading to a general, toxic-reagent-free synthesis of C-glycosides of 2-deoxy-2-amino sugars. The reaction is 1,2-trans-stereoselective and can utilize aryl alkenes as substrates. Late-stage functionalization and density functional theory calculations have been reported.
Article
Cell Biology
Patrycja Szczupak, Malgorzata Sierant, Ewelina Wielgus, Ewa Radzikowska-Cieciura, Katarzyna Kulik, Agnieszka Krakowiak, Paulina Kuwerska, Grazyna Leszczynska, Barbara Nawrot
Summary: This study characterized the substrate requirements of the bacterial enzyme SelU, identified SelU-associated tRNAs and their specific modifications in the wobble position. It explained the sequence of steps in the selenation of tRNA and found that the recognition by SelU is influenced by the S2U position within the RNA chain, the flanking sequence of the modification, and the length of the RNA substrate.
Article
Chemistry, Organic
Tomas Lasek, Juraj Dobias, Milos Budesinsky, Jaroslav Kozak, Barbora Lapunikova, Ivan Rosenberg, Gabriel Birkus, Ondrej Pav
Summary: This study describes a new synthetic route for fluorinated nucleoside analogs and a universal synthetic route for nucleosides bearing purine nucleobases. The compounds were evaluated for inhibitory potency against viral polymerases and tested in cell cultures against various viruses, including influenza and SARS-CoV-2.
Article
Biochemistry & Molecular Biology
Patrycja Szczupak, Ewa Radzikowska-Cieciura, Katarzyna Kulik, Rafal Madaj, Malgorzata Sierant, Agnieszka Krakowiak, Barbara Nawrot
Summary: The bacterial tRNA 2-selenouridine synthase SelU shows high substrate specificity for geranyl pyrophosphate in the prenylation reaction, while there is little discrimination in the selenation reaction. It is suggested that only geranyl pyrophosphate and geranylated tRNA serve as substrates for the conversion of 2-thio-tRNAs to 2-seleno-tRNAs in the bacterial system.
BIOORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Mieke Guinan, Ningwu Huang, Mark Smith, Gavin J. Miller
Summary: The study developed a new class of nucleoside analogues with good activity against Hepatitis C replicon, which is significant in the field of antiviral drug research.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Mikhail S. Drenichev, Vladimir E. Oslovsky, Anastasia A. Zenchenko, Claudia V. Danilova, Mikhail A. Varga, Roman S. Esipov, Dmitry D. Lykoshin, Cyril S. Alexeev
Summary: A comparative analysis was conducted on the transglycosylation conditions catalyzed by E. coli nucleoside phosphorylases, leading to the formation of 2'-deoxynucleosides. The study demonstrated that maximal yields of modified 2'-deoxynucleosides can be achieved with a slight excess of carbohydrate residue donor nucleoside and a four-fold lack of phosphate.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Isabel Thiele, Heba Yehia, Niels Krausch, Mario Birkholz, Mariano Nicolas Cruz Bournazou, Azis Boing Sitanggang, Matthias Kraume, Peter Neubauer, Anke Kurreck
Summary: Nucleoside analogues are important for treating viral infections or cancers. Continuous enzyme membrane reactors (EMRs) offer an alternative to batch enzymatic reactions, allowing for continuous production with integrated biocatalyst separation. The EMR demonstrated comparable specific productivities to batch reactions, but with significantly higher product per enzymatic unit for all nucleosides synthesized. This study validates the application of EMRs for nucleoside synthesis, reducing production costs and improving downstream processing.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Physical
Daniel Baranowski, Adam Mieczkowski, Damian Trzybinski, Krzysztof Wozniak, Katarzyna Bednarska-Szczepaniak, Zofia Gdaniec, Zbigniew J. Lesnikowski
Summary: Detailed studies using NMR, crystallography, and ab initio methods were conducted on boron cluster-modified adenosine and 2'-deoxyadenosine derivatives, revealing consistent results. Introduction of bulky substituents at position C8 of adenosine resulted in increased population of syn conformation around the glycosidic bond, accompanied by a predominance of the South-type conformation and the presence of the + sc rotamer. Intramolecular hydrogen bond formation between 5 ' O -H and N3 was observed due to the coexistence of syn conformation, South-type conformation, and + sc rotamer. The crystal structures of adenosine-boron cluster derivatives were reported for the first time.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Biochemistry & Molecular Biology
Katja F. Hellendahl, Felix Kaspar, Xinrui Zhou, Zhaoyi Yang, Zhen Huang, Peter Neubauer, Anke Kurreck
Summary: By optimizing the synthesis of selenium-modified nucleosides using thermostable nucleoside phosphorylases in transglycosylation reactions with natural nucleosides as sugar donors, the study achieved isolated yields of Se-containing nucleosides in 6-40%. However, the unfavorable thermodynamic properties of the nucleosides required a tenfold excess of sugar donor for conversion, complicating the synthesis process.
Article
Chemistry, Organic
Kasper M. Beck, Poul Nielsen
Summary: By modifying nucleotides, synthetic nucleic acids have been applied in various fields of biotechnology and the pharmaceutical industry. This study introduces a 2'-deoxy version of the BX design (dSBX) with the purpose of improving RNA recognition. The dSBX design was found to engage in reverse Watson-Crick pairing using its 2'-base and form stable base pairs with specific nucleobases.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Haidong Teng, Zhige Wu, Ziyuan Wang, Zhihua Jin, Yu Yang, Qingchao Jin
Summary: Nucleoside analogs are commonly used for cancer and viral infections treatment. Purine nucleoside phosphorylase (PNP) is a key enzyme in the biosynthesis of 2'-deoxy-2'-fluoroadenosine. Mutations in PNP were selected based on molecular docking and dynamic simulations, leading to an increase in enzymatic activity and improved synthesis of 2'-deoxy-2'-fluoroadenosine.
PROCESS BIOCHEMISTRY
(2021)
Article
Chemistry, Physical
Srishylam Penjarla, Paidi Yella Reddy, Santhosh Penta, Yogesh S. Sanghvi, Ludek Eyer, Michal Stefanik, Daniel Ruzek, Shyamapada Banerjee
Summary: An efficient synthetic approach leading to novel C-nucleosides containing oxadiazole or thiadiazole ring system is reported. This provides an ideal framework for the development of new antiviral and antitumor drugs. Two of the synthesized compounds showed mild anti-SARS-CoV-2 activity, with a decrease in viral titers by <1 log10 PFU/ml compared with controls. Mechanism for the formation of 5-substituted 1,3,4-thiadiazole ring is proposed and a structure-activity relationship is established with these C-nucleosides.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Article
Chemistry, Medicinal
Jiao Hou, Youmei Peng, Bingjie Liu, Qianqian Zhang, Jian-Hua Wang, Wenquan Yu, Junbiao Chang
Summary: 2'-Deoxy-2'-β-fluoroadenosines with 4'-azido or 4'-ethynyl groups have been synthesized for the treatment of HIV-1 infection. These compounds exhibit nanomolar anti-HIV-1 activity, with the 4'-ethynyl-2-fluoroadenosine analog 1c (CL-197) being the most potent and least cytotoxic (EC50 = 0.9 nM, CC50 > 100 μM). It shows strong inhibitory activity against drug resistant and clinical HIV-1 strains. Oral administration of 1c in Beagle dogs results in high levels of the bioactive form 1c-TP in peripheral blood mononuclear cells, where it exhibits long-term intracellular retention and prevents HIV-1 infection for an extended time. 1c displays low in vivo toxicity and favorable pharmacokinetic profiles in Sprague-Dawley rats. The preclinical data support the further development of 1c as a highly potent and orally bioavailable clinical candidate for treating HIV-1 infection. Currently, CL-197 is in clinical trials in China (registration number: CXHL2200529).
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Byeong-il Kang, Kenjyo Miyauchi, Michal Matuszewski, Gabriel Silveira D'Almeida, Mary Anne T. Rubio, Juan D. Alfonzo, Kazuki Inoue, Yuriko Sakaguchi, Takeo Suzuki, Elzbieta Sochacka, Tsutomu Suzuki
NUCLEIC ACIDS RESEARCH
(2017)
Article
Biochemistry & Molecular Biology
Michal Matuszewski, Jakub Wojciechowski, Kenjyo Miyauchi, Zofia Gdaniec, Wojciech M. Wolf, Tsutomu Suzuki, Elzbieta Sochacka
NUCLEIC ACIDS RESEARCH
(2017)
Article
Biochemistry & Molecular Biology
Malgorzata Sierant, Katarzyna Kulik, Elzbieta Sochacka, Rafal Szewczyk, Milena Sobczak, Barbara Nawrot
Article
Biochemistry & Molecular Biology
Malgorzata Sierant, Grazyna Leszczynska, Klaudia Sadowska, Patrycja Komar, Ewa Radzikowska-Cieciura, Elzbieta Sochacka, Barbara Nawrot
Article
Biochemistry & Molecular Biology
L. Peter Sarin, Sandra D. Kienast, Johannes Leufken, Robert L. Ross, Agnieszka Dziergowska, Katarzyna Debiec, Elzbieta Sochacka, Patrick A. Limbach, Christian Fufezan, Hannes C. A. Drexler, Sebastian A. Leidel
Article
Chemistry, Multidisciplinary
Katarzyna Debiec, Michal Matuszewski, Karolina Podskoczyj, Grazyna Leszczynska, Elzbieta Sochacka
CHEMISTRY-A EUROPEAN JOURNAL
(2019)
Article
Biochemistry & Molecular Biology
Grazyna Leszczynska, Marek Cypryk, Bartlomiej Gostynski, Klaudia Sadowska, Paulina Herman, Grzegorz Bujacz, Elzbieta Lodyga-Chruscinska, Elzbieta Sochacka, Barbara Nawrot
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Review
Biochemistry & Molecular Biology
Karolina Bartosik, Katarzyna Debiec, Anna Czarnecka, Elzbieta Sochacka, Grazyna Leszczynska
Article
Biochemistry & Molecular Biology
Katarzyna Kulik, Klaudia Sadowska, Ewelina Wielgus, Barbara Pacholczyk-Sienicka, Elzbieta Sochacka, Barbara Nawrot
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Katarzyna Frankowska, Elzbieta Sochacka
Summary: A novel and efficient method for synthesizing N-6-hydantoin-modified adenosines has been developed. The method utilizes readily available adenosine derivatives and involves a series of reactions to obtain the desired products.
Article
Biochemistry & Molecular Biology
Katarzyna Kulik, Klaudia Sadowska, Ewelina Wielgus, Barbara Pacholczyk-Sienicka, Elzbieta Sochacka, Barbara Nawrot
Summary: The 2-selenouridine component of tRNA is more susceptible to oxidation and exhibits antioxidant potential in cells. Additionally, new oligomeric nucleosides are formed during the oxidation process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
M. Sierant, R. Szewczyk, K. Krolewska-Golinska, A. Dziergowska, P. Bernat, E. Sochacka, B. Nawrot
Article
Chemistry, Multidisciplinary
Katarzyna Debiec, Elzbieta Sochacka
Summary: An efficient method of ureido linkage formation was developed for the epimerization-free one-pot synthesis of protected hypermodified N-6-threonylcarbamoyladenosine and its 2-SMe analog. Starting from different protected adenosine derivatives, the corresponding 3'-O-phosphoramidite monomers were successfully obtained.
Article
Chemistry, Multidisciplinary
Robert Borowski, Agnieszka Dziergowska, Elzbieta Sochacka, Grazyna Leszczynska
Meeting Abstract
Biochemistry & Molecular Biology
M. Sierant, R. Szewczyk, A. Dziergowska, K. Krolewska-Golinska, E. Sochacka, B. Nawrot