Article
Chemistry, Medicinal
Xia Lin, Chunxian Liang, Lianjia Zou, Yanchun Yin, Jianyi Wang, Dandan Chen, Weisen Lan
Summary: Different modifications of the sugar and base in nucleoside drugs can affect their bioactivity, with certain groups enhancing anti-tumor or antiviral effects. Macromolecule-modified nucleosides can improve bioavailability and bioactivity, while reducing toxicity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Physical
Jie Lv, Juan Zou, Yingling Nong, Jia Song, Tingwei Shen, Hui Cai, Chengli Mou, Wenxin Lyu, Zhichao Jin, Yonggui Robin Chi
Summary: Nucleosides have therapeutic applications against COVID viruses. Converting hydroxyl units in nucleosides to ester groups is a common strategy for preparing nucleoside prodrugs. However, this process usually involves multiple steps. A new catalytic strategy allows for selective acylation of a specific OH unit in nucleosides, simplifying the preparation of prodrugs such as molnupiravir.
Article
Chemistry, Inorganic & Nuclear
Joanna Skiba, Aleksandra Kowalczyk, Damian Trzybinski, Krzysztof Wozniak, Valerije Vrcek, Magdalena Gapinska, Konrad Kowalski
Summary: This paper reports a Yb(OTf)(3)-mediated etherification reaction to obtain R,R and S,R isomers of ferrocenyl glycol nucleic acid (Fc-GNA) nucleosides from their stereo-defined (S,R) precursor. The mechanism of the reaction is explained by density functional theory calculations, and the obtained compounds show reversible oxidation of the ferrocenyl portion. Anticancer activity studies reveal that the (S,R) nucleoside exhibits the highest activity against cancer cells HeLa and Ishikawa, inducing apoptosis in HeLa cells at a concentration of IC50=66.0 μM after 72 hours of treatment.
EUROPEAN JOURNAL OF INORGANIC CHEMISTRY
(2021)
Review
Food Science & Technology
Ting Ding, Ge Song, Xinran Liu, Meihong Xu, Yong Li
Summary: Nucleotides are the basic units of nucleic acid macromolecules, playing important physiological and biochemical functions in organisms. Recent studies have shown that exogenous nucleotides are essential nutrients under specific physiological conditions, entering tissues, reducing the body's synthesis needs, and enhancing immune function and regulating intestinal flora.
JOURNAL OF FUNCTIONAL FOODS
(2021)
Article
Chemistry, Medicinal
Michaela Serpi, Valentina Ferrari, Christopher McGuigan, Essam Ghazaly, Chris Pepper
Summary: We report NUC-7738 (7a), a 5'-aryloxy phosphoramidate prodrug of 3'-deoxyadenosine, which showed effective anticancer activity against various cancer cell lines, particularly leukemic stem cells. Unlike 3'-dA, the activity of 7a was independent of cellular transporters and kinases, and it exhibited resistance to metabolic deactivation.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Chenglong Zhao, Xiao Jia, Dominique Schols, Jan Balzarini, Chris Meier
Summary: This study presents the design of new nucleoside analogue derivatives with the aim of developing more effective anti-HIV drugs. These compounds were shown to be active against HIV in cell culture experiments, and the hydrolysis of the prodrug masks was investigated.
Article
Chemistry, Multidisciplinary
Jianyang Han, Jakob Arnold, Christophe Pannecouque, Graciela Andrei, Robert Snoeck, Clemens Richert
Summary: Strongly pairing ethynylpyridone C-nucleosides are being explored as substitutes for thymidine in oligonucleotides. However, the strong lipophilicity of ethynylpyridone has been found to limit its antiviral activity. Two strategies are being pursued to overcome this issue, including replacing the ethynyl group with a cyano group and using less lipophilic amino acid esters in a phosphoramidate prodrug design. These findings contribute to the development of next-generation pyridone C-nucleosides as potential antivirals.
HELVETICA CHIMICA ACTA
(2023)
Article
Chemistry, Organic
Zackery W. Dentmon, Christopher J. Butch, Hannah B. Gold, Dennis C. Liotta
Summary: The energetic conformational bias of nucleoside metabolites is closely related to their antiviral activity. Manipulating the conformational bias by substituting the ribofuranose ring can affect the activity. However, the computational model did not accurately predict the antiviral activity, indicating the need for further refinement considering other biostructural factors.
Article
Chemistry, Multidisciplinary
Juri Eyberg, Mark Ringenberg, Clemens Richert
Summary: A new type of deoxynucleoside was reported in this study, which can control the pairing strength of nucleobases in DNA through reactions with compounds found inside the cell. The deoxynucleoside exhibits reactivity towards soft nucleophiles, changes its fluorescence, and has potential applications in controlled release, chemical biology, sensing, and diagnostics.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Organic
Jennifer Albaneze-Walker, Gregor Urbanietz, Andras Horvath, Stefano Lancianesi, Alejandro Gimenez Molina, Thomas De Vijlder, Mattijs Baeten, Martine Canters
Summary: Azido nucleosides can be coupled with phosphoramidites via an initial iminophosphorane reaction, generating a coupled dimer P(V) product by eliminating acrylonitrile. This method bypasses the susceptible phosphite triester intermediate, making it suitable for solution-phase synthesis. It provides a new approach for installing internucleosidic phosphorodiamidate bonds with nearly quantitative yields, without the need for protection of the 5'-OH function.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Maria De Fenza, Anna Esposito, Giovanni Talarico, Graciela Andrei, Robert Snoeck, Daniele D'Alonzo, Annalisa Guaragna
Summary: In this study, six-membered nucleoside analogues with a piperidine ring as the preorganized (deoxy)ribose bioisostere were synthesized and evaluated for their antiviral activity. The 5-iododeoxyuridine analogue showed activity against all tested DNA viruses. DFT analysis and pH-dependent NMR experiments suggested that the antiviral activity was attributed to the biomimetic character of the piperidine ring, which can mimic the conformation of natural nucleosides when interacting with viral enzymes.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
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
Samir Mohamed Awad, Shima Mahmoud Ali, Yara Essam Mansour, Samar Said Fatahala
Summary: Newly synthesized nucleoside drugs show promising activity against HSV-1, offering a potential solution to the problems associated with current medications.
Article
Food Science & Technology
Jianshuang Zhang, Na Wang, Wanxuan Chen, Weiping Zhang, Haoshen Zhang, Hao Yu, Yin Yi
Summary: This study used untargeted metabolomics and transcriptomics to uncover the differences in accumulated metabolites and expressed genes between wild and cultivated O. sinensis. The results showed that the two types of O. sinensis had differences in amino acid metabolism, plant secondary metabolite biosynthesis, and purine nucleotide metabolism. Integrated metabolomics and transcriptomics analyses identified several genes that may be related to the synthesis of purine nucleotides and nucleosides.
FOOD RESEARCH INTERNATIONAL
(2023)
Editorial Material
Chemistry, Medicinal
Carlo Ballatore
Summary: The study demonstrates that replacing the pro-moiety structure can significantly improve the antiviral activity and selectivity index of acyclic nucleoside phosphonate, which is of great significance for the development of new drugs.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Erica Barini, Ageo Miccoli, Federico Tinarelli, Katie Mulholland, Hachemi Kadri, Farhat Khanim, Laste Stojanovski, Kevin D. Read, Kerry Burness, Julian J. Blow, Youcef Mehellou, Miratul M. K. Muqit
Article
Chemistry, Medicinal
Martin S. Davey, Roshni Malde, Rory C. Mykura, Alfie T. Baker, Taher E. Taher, Cecile S. Le Duff, Benjamin E. Willcox, Youcef Mehellou
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Multidisciplinary Sciences
Fabio Giuseppe Liberante, Katrina Lappin, Eliana M. Barros, Jekaterina Vohhodina, Florian Grebien, Kienan Savage, Kenneth Ian Mills
SCIENTIFIC REPORTS
(2019)
Article
Hematology
Stephanie Jordaens, Leah Cooksey, Stephanie Bonney, Laurence Orchard, Matthew Coutinho, Viggo Van Tendeloo, Ken I. Mills, Kim Orchard, Barbara-ann Guinn
BRITISH JOURNAL OF HAEMATOLOGY
(2020)
Review
Oncology
Stephanie Jordaens, Leah Cooksey, Laurie Freire Boullosa, Viggo Van Tendeloo, Evelien Smits, Ken I. Mills, Kim H. Orchard, Barbara-ann Guinn
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2020)
Article
Hematology
Samah Alimam, William Villiers, Richard Dillon, Michael Simpson, Manohursingh Runglall, Alexander Smith, Prodromos Chatzikyriakou, Paul Lavender, Anju Kanda, Ken Mills, Beatriz Bellosillo Paricio, James Kaufman-Cook, Sophie Ord, Shahram Kordasti, Deepti Radia, Claire Woodley, Yvonne Francis, Ghulam Mufti, Donal P. McLornan, Claire N. Harrison
Summary: The study identified similar patterns of gene expression and DNA methylation in patients with essential thrombocythemia (ET) with known driver mutations and those with triple-negative disease, suggesting that the ET phenotype may be primarily driven by transcriptional misregulation and may propagate downstream via MAPK, tumor necrosis factor, and NF kappa B pathways. These findings highlight potential novel mechanisms of disease initiation that require further evaluation.
Article
Biochemistry & Molecular Biology
Lauren Cairns, Katrina M. Lappin, Alexander Mutch, Ahlam Ali, Kyle B. Matchett, Ken Mills
Summary: Paediatric acute myeloid leukaemia (AML) is a complex disease with limited treatment options due to longstanding standard therapies and inadequate understanding of its biology. Recent advancements in genomic technologies have accelerated the search for new targets for paediatric AML treatment. Exploiting drug combinations through innovative screening strategies may offer new therapeutic options for paediatric AML.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Katrina M. Lappin, Eliana M. Barros, Satpal S. Jhujh, Gareth W. Irwin, Hayley McMillan, Fabio G. Liberante, Cheryl Latimer, Melissa J. La Bonte, Ken Mills, D. Paul Harkin, Grant S. Stewart, Kienan Savage
Summary: Mutations in SF3B1 affect cellular response to DNA damage and increase sensitivity to ionizing radiation and chemotherapeutic agents. These mutations induce DNA damage and can be targeted with PARP inhibitors.
Article
Biochemistry & Molecular Biology
Jochen Greiner, Elliott Brown, Lars Bullinger, Robert K. Hills, Vanessa Morris, Hartmut Doehner, Ken I. Mills, Barbara-ann Guinn
Summary: This study found that BIRC5 expression plays a role in the survival of AML patients, with above median levels associated with improved overall survival but not reaching statistical significance. Adjusted analyses showed a beneficial effect of high BIRC5 levels on overall survival. Additionally, decreased BIRC5 expression was associated with better clinical outcome.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Andrew Hindley, Mark Alexander Catherwood, Mary Frances McMullin, Ken Mills
Summary: This literature review examines the significance of the NPM1 gene in acute myeloid leukaemia, including its structure, mutations, and impact on AML development. The importance of NPM1 mutations on prognosis and treatment options are discussed, as well as the guidelines recommending rapid return of screening results and suitable laboratory assays. Future developments in targeting NPM1 mutated AML are also considered.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Virology
Connor G. G. Bamford, Lindsay Broadbent, Elihu Aranday-Cortes, Mary McCabe, James McKenna, David G. Courtney, Olivier Touzelet, Ahlam Ali, Grace Roberts, Guillermo Lopez Campos, David Simpson, Conall McCaughey, Derek Fairley, Ken Mills, Ultan F. Power
Summary: This study finds that the evolution of SARS-CoV-2 is restrained in pediatric respiratory epithelial cells but still exhibits significant genetic plasticity shaped by both viral and host cell factors.
Article
Biochemistry & Molecular Biology
Viktoriya B. Boncheva, Michael Linnebacher, Said Kdimati, Hannah Draper, Laurence Orchard, Ken Mills, Gerald O'Sullivan, Mark Tangney, Barbara-Ann Guinn
Summary: A Crohn's-like lymphoid reaction (CLR) is observed in about 15% of colorectal cancer (CRC) patients and is associated with favourable outcomes. By immunoscreening, the heavy chain of IgG3 (IGHG3) and a novel antigen named UOB-COL-7 were solely recognised by sera from CRC CLR patients. These findings demonstrate the potential of SEREX-identified CRC CLR antigens to act as biomarkers for CRC.
Article
Biochemistry & Molecular Biology
Ahlam A. Ali, Lauren V. Cairns, Kathryn M. Clarke, Jaine K. Blayney, Katrina M. Lappin, Ken I. Mills
Summary: Paediatric acute myeloid leukaemia (AML) poses challenges in treatment, and there is no standard approach for young patients. Combination therapies that target multiple pathways could be a promising treatment option. Through in silico analysis, we identified cell death and survival as a potential target in paediatric AML and discovered novel drug combinations, such as ABT-737 + Purvalanol-A and ABT-737 + AKT inhibitor + SU9516, that showed significant synergism in AML cell lines. Our findings provide insights into potential combination treatments for AML.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Hematology
Maryam Ahmed S. Al Barashdi, Ahlam Ali, Mary Frances Mcmullin, Ken Mills
Summary: This study found that inhibition of CD45 could increase the sensitivity of cells to common chemotherapy drugs in myeloid malignancies, leading to improved treatment efficacy. Bioinformatics analysis also identified genes and drugs correlated with CD45 expression, which could serve as potential CD45 inhibitors. Therefore, CD45 inhibition may be a promising therapeutic approach for the treatment of myeloid malignancies.
ANNALS OF HEMATOLOGY
(2023)
Article
Multidisciplinary Sciences
Fatemeh Mirzadeh Azad, Eduard A. Struys, Victoria Wingert, Luciana Hannibal, Ken Mills, Joop H. Jansen, Daniel B. Longley, Hendrik G. Stunnenberg, Yaser Atlasi
Summary: Understanding the mechanisms of epigenetic regulation in ESCs is crucial for stem cell and developmental biology. In this study, the identification of Spic as a marker of ground state pluripotency and its role in controlling 1C metabolism and histone marks highlight the importance of auxiliary TFs in linking cellular metabolism to epigenetic regulation in ESCs.