Article
Biochemistry & Molecular Biology
Ilja V. Fateev, Maria A. Kostromina, Yuliya A. Abramchik, Barbara Z. Eletskaya, Olga O. Mikheeva, Dmitry D. Lukoshin, Evgeniy A. Zayats, Maria Ya. Berzina, Elena V. Dorofeeva, Alexander S. Paramonov, Alexey L. Kayushin, Irina D. Konstantinova, Roman S. Esipov
Summary: A comparative study was conducted on the use of ribokinase -> phosphopentomutase -> nucleoside phosphorylase cascades in the synthesis of modified nucleosides. Recombinant phosphopentomutase from Thermus thermophilus HB27 was obtained for the first time, and it was found that performing the cascade reactions with Escherichia coli enzymes resulted in significantly higher product formation rates and content of target products in the reaction mixture.
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
Pharmacology & Pharmacy
Natale Belluardo, Giuseppa Mudo, Valentina Di Liberto, Monica Frinchi, Daniele F. Condorelli, Ugo Traversa, Francisco Ciruela, Renata Ciccarelli, Patrizia Di Iorio, Patricia Giuliani
Summary: The study found that guanosine can promote neuroblastoma cell differentiation by inducing neuron-like cell differentiation, mainly through an extracellular pathway. This differentiation process was found to be independent of adenosine receptor activation, but was influenced by inhibitors of protein kinase C or soluble guanylate cyclase.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Danielle Figueredo da Silva, Jessica Lima de Souza, Diego Mota da Costa Jr, David Bacelar Costa, Paulo Otavio Lourenco Moreira, Amanda Luisa da Fonseca, Fernando de Pilla Varotti, Jorddy Neves Cruz, Cleydson Breno Rodrigues dos Santos, Clayton Queiroz Alves, Franco Henrique Andrade Leite, Hugo Neves Brandao
Summary: This study aimed to evaluate the antiplasmodial activity of auraptene and poligalen against a chloroquine-resistant strain of Plasmodium falciparum. The results showed that auraptene and poligalen exhibited antiplasmodial activity against Plasmodium falciparum, with high selectivity indexes. Molecular dynamics studies demonstrated the stability of coumarins at the binding site and favorable binding energies.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Anastasia Khandazhinskaya, Ilja Fateev, Barbara Eletskaya, Anna Maslova, Irina Konstantinova, Katherine Seley-Radtke, Sergey Kochetkov, Elena Matyugina
Summary: The structure of human purine nucleoside phosphorylase (hPNP) is of great interest due to its significance in the therapy of T-cell proliferative diseases. Additionally, hPNP inhibitors are used in organ transplant surgeries to provide immunodeficiency. Fleximer compounds have shown promise as substrates of hPNP and exhibit biological activity against viruses. In this study, we synthesized and tested a series of fleximer compounds as hPNP inhibitors and investigated their binding mode with the enzyme.
Review
Peripheral Vascular Disease
Edwin K. Jackson, Stevan P. Tofovic, Yuanyuan Chen, Lori A. Birder
Summary: 8-Aminoguanosine and 8-aminoguanine have diuretic and natriuretic effects, but decrease potassium excretion. Their mechanism of action involves the inhibition of PNPase, leading to increased renal interstitial inosine levels. Inosine, through adenosine A2B receptor activation, enhances renal excretory function by increasing renal medullary blood flow. Additionally, 8-aminoguanine has pleiotropic actions that affect renal excretory function.
Article
Peripheral Vascular Disease
Edwin K. Jackson, Delbert G. Gillespie, Zaichuan Mi
Summary: The endogenous purine 8-aminoguanine causes diuresis/natriuresis/glucosuria by inhibiting PNPase (purine nucleoside phosphorylase); however, the specific mechanisms have been previously unknown. This study investigated the effects of 8-aminoguanine on renal excretory function using various techniques and found that it increases renal interstitial levels of inosine, which in turn activates A(2B) receptors and enhances renal excretory function, potentially through increased medullary blood flow.
Article
Chemistry, Multidisciplinary
Anastasia Khandazhinskaya, Ilja Fateev, Irina Konstantinova, Roman Esipov, Konstantin Polyakov, Katherine Seley-Radtke, Sergey Kochetkov, Elena Matyugina
Summary: A series of new 5'-norcarbocyclic nucleoside and aza/deaza-purine nucleoside analogs were synthesized and evaluated as potential inhibitors of E. coli purine nucleoside phosphorylase. The compounds showed inhibitory effects, but only when a cyclopentyl moiety was present at specific positions.
FRONTIERS IN CHEMISTRY
(2022)
Article
Engineering, Environmental
Valentina I. Merkus, Michael S. Leupold, Sarah P. Rockel, Holger Lutze, Torsten C. Schmidt
Summary: The ozonation of micropollutants is greatly influenced by the composition of water, particularly the presence of natural organic matter and carbonate species. In this study, the degradation and product formation of purine derivatives, which are common antiviral micropollutants, were investigated in different artificial water matrices, with a focus on the impact of natural organic matter and alkalinity. It was found that the presence of bicarbonate in the water matrix inhibited the degradation of purine and adenine due to the scavenging of hydroxyl radicals. However, the formation of carbonate radicals contributed to the degradation of compounds and affected the stability of transformation products, especially in high alkalinity conditions.
Article
Biochemistry & Molecular Biology
Alexey L. Kayushin, Julia A. Tokunova, Ilja V. Fateev, Alexandra O. Arnautova, Maria Ya. Berzina, Alexander S. Paramonov, Olga I. Lutonina, Elena V. Dorofeeva, Konstantin V. Antonov, Roman S. Esipov, Igor A. Mikhailopulo, Anatoly I. Miroshnikov, Irina D. Konstantinova
Summary: This study investigates the issues encountered during the preparative synthesis of 2-fluorocordycepin, as well as the impact of unknown nucleoside formation on the reaction. The hydrolysis mechanism of 2',3'-anhydroinosine in D2O is fully determined for the first time in this research, shedding light on its inhibitory effects on the synthesis of 2-fluorocordycepin.
Article
Medicine, Research & Experimental
Stevan P. Tofovic
Summary: Under hemolytic conditions, interaction among RBCs, ECs, and platelets plays a significant role in SCD, leading to vasoocclusive crisis and organ damage. These cells share biochemical properties relevant to SCD, such as high PNP levels and glycolytic metabolism. PNP activity and glycolysis promote RBC sickling/hemolysis, oxidative vascular injury, and platelet activation/aggregation in SCD.
MEDICAL HYPOTHESES
(2023)
Article
Biochemistry & Molecular Biology
Vladimir I. Timofeev, Ilya V. Fateev, Maria A. Kostromina, Yuliya A. Abramchik, Irina D. Konstantinova, Vladimir V. Volkov, Dmitry D. Lykoshin, Olga O. Mikheeva, Tatiana I. Muravieva, Roman S. Esipov, Inna P. Kuranova
Summary: Two recombinant purine nucleoside phosphorylases from Thermus thermophilus HB27 were purified and characterized. TthPNPI is specific to guanosine while TthPNPII is specific to adenosine. The oligomeric structures of these enzymes, as well as the key residues in their active sites, were analyzed. The crystal structure of TthPNPII was determined and its active site cavity was examined. The hexameric structure of TthPNPII, which is different from other purine nucleoside phosphorylases, was observed for the first time.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemical Research Methods
I. A. T. Ximenes, M. Albino, C. Sangregorio, Q. B. Cass, M. C. de Moraes
Summary: This study developed enzymatic assays for screening HsPNP inhibitors, with offline HPLC-DAD assessment and high-throughput on-flow method. The results validated the effectiveness and feasibility of the assays, demonstrating their potential for selective recognition and characterization of HsPNP inhibitors.
JOURNAL OF CHROMATOGRAPHY A
(2022)
Article
Urology & Nephrology
Lori A. Birder, Amanda Wolf-Johnston, Alan J. Wein, Mara Grove-Sullivan, Donna Stoltz, Simon Watkins, Diane Newman, Roger R. Dmochowski, Edwin K. Jackson
Summary: Aging increases oxidative stress, leading to bladder dysfunction in elderly women. 8-aminoguanine (8-AG) has the potential to restore urethra and external sphincter muscle morphology in aged rats, suggesting therapeutic implications for age-related urinary incontinence.
WORLD JOURNAL OF UROLOGY
(2021)
Article
Chemistry, Organic
Anastasia Khandazhinskaya, Barbara Eletskaya, Ilja Fateev, Maria Kharitonova, Irina Konstantinova, Vladimir Barai, Alex Azhayev, Mervi T. Hyvonen, Tuomo A. Keinanen, Sergey Kochetkov, Katherine Seley-Radtke, Alex Khomutov, Elena Matyugina
Summary: Nucleoside analogues have been crucial in treating viral infections and cancers, with researchers developing new fleximer nucleosides by splitting the purine base into pyrimidine and imidazole components. Studies have shown that pyrazole-containing flex-bases can serve as substrates for purine nucleoside phosphorylase (PNP), providing a potential solution to drug resistance issues.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Editorial Material
Pharmacology & Pharmacy
Caio M. Massari, Mariachiara Zuccarini, Patrizia Di Iorio, Carla I. Tasca
FRONTIERS IN PHARMACOLOGY
(2021)
Editorial Material
Pharmacology & Pharmacy
Sarah Beggiato, Mariachiara Zuccarini, Tommaso Cassano, Dasiel Oscar Borroto-Escuela, Patrizia Di Iorio, Robert Schwarcz, Kjell Fuxe, Luca Ferraro
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Vanni Caruso, Mariachiara Zuccarini, Patrizia Di Iorio, Ishaq Muhammad, Maurizio Ronci
Summary: This review discusses the molecular mechanisms leading to changes in feeding behavior within hypothalamic neurons following purinergic receptor activation, emphasizes the importance of purinergic signaling in metabolic homeostasis, and explores the possibility of targeting its receptors for therapeutic purposes.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Mariachiara Zuccarini, Patricia Giuliani, Valentina Di Liberto, Monica Frinchi, Francesco Caciagli, Vanni Caruso, Renata Ciccarelli, Giuseppa Mudo, Patrizia Di Iorio
Summary: In the past decade, several compounds have been identified for treating obesity, but concerns about their efficacy and safety remain due to the complexity of the disease. Therefore, it is crucial to discover new factors involved in obesity induction and progression. Adipose stromal/stem cells release extracellular vesicles (EVs), which play an important role in regulating metabolic processes. However, there are advantages and disadvantages to using EVs as potential next-generation anti-obesity agents.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Patrizia Di Iorio, Maurizio Ronci, Patricia Giuliani, Francesco Caciagli, Renata Ciccarelli, Vanni Caruso, Sarah Beggiato, Mariachiara Zuccarini
Summary: The cyclic nucleotides, cAMP and cGMP, act as second messengers in both normal and tumor cells, playing a crucial role in translating extracellular signals to intracellular responses. Inhibition of cGMP-hydrolyzing phosphodiesterases (PDEs) has shown potential as a therapeutic approach for cancer by regulating cell growth, apoptosis, and sensitivity to chemotherapy. However, the use of PDE5 inhibitors in breast cancer treatment remains controversial.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Mariachiara Zuccarini, Patricia Giuliani, Maurizio Ronci, Francesco Caciagli, Vanni Caruso, Renata Ciccarelli, Patrizia Di Iorio
Summary: The role of purinergic signal in the oral cavity and its potential application in oral diseases are discussed, highlighting the need for further research to translate the findings into clinical practice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Daniela Passarella, Silvia Ciampi, Valentina Di Liberto, Mariachiara Zuccarini, Maurizio Ronci, Alessandro Medoro, Emanuele Fodera, Monica Frinchi, Donatella Mignogna, Claudio Russo, Carola Porcile
Summary: The low-density-lipoprotein receptors, including LRP8, play a crucial role in lipid homeostasis, cell migration, proliferation, and differentiation, and are involved in both cancer and neurodegenerative diseases. LRP8 is overexpressed in various types of cancer and also has potential roles in neurodegeneration, acting as a receptor for ApoE and reelin, and a substrate for gamma-secretase.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Daniela Passarella, Maurizio Ronci, Valentina Di Liberto, Mariachiara Zuccarini, Giuseppa Mudo, Carola Porcile, Monica Frinchi, Patrizia Di Iorio, Henning Ulrich, Claudio Russo
Summary: Recent studies have found that cerebral cholesterol formation is primarily controlled by astrocytes, which synthesize cholesterol and deliver it to neurons and oligodendrocytes through specific lipoprotein receptors. Various proteins and carbohydrates modulate the cholesterol shuttle, affecting lipoprotein receptor activity, function, and signaling. Purine receptors, particularly subtypes P2Y(2), P2X(7), and A(2A), play a role in neurodegenerative diseases such as Alzheimer's and Niemann-Pick C diseases by regulating brain cholesterol homeostasis. The precise mechanisms of these interactions are not well understood, but further research in the cholesterol-purine reciprocal control is warranted.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Laura Giusti, Marta Tesi, Federica Ciregia, Lorella Marselli, Lorenzo Zallocco, Mara Suleiman, Carmela De Luca, Silvia Del Guerra, Mariachiara Zuccarini, Marco Trerotola, Decio L. Eizirik, Miriam Cnop, Maria R. Mazzoni, Piero Marchetti, Antonio Lucacchini, Maurizio Ronci
Summary: Metformin was found to alleviate human beta-cell stress induced by pro-inflammatory cytokines, leading to proteome modifications in human islets.
Article
Cell Biology
Domenico Nuzzo, Monica Frinchi, Costanza Giardina, Miriana Scordino, Mariachiara Zuccarini, Chiara De Simone, Marta Di Carlo, Natale Belluardo, Giuseppa Mudo, Valentina Di Liberto
Summary: Alzheimer's disease is a multifactorial and age-related neurodegenerative disorder. Its pathogenesis is associated with senile plaques, neurofibrillary tangles, oxidative stress, and neuroinflammation. Current therapies have limited effectiveness, and research on disease-modifying treatments is ongoing. Previous studies have shown that Oxo, a muscarinic acetylcholine receptor agonist, has neurotrophic effects and can modulate oxidative stress and neuroinflammation in the brain. This study investigated the neuroprotective effects of Oxo in an in vitro model of AD, and found that it enhanced cell survival, neurite length, and counteracted DNA fragmentation caused by A beta(1-42) peptide. Oxo treatment also blocked oxidative stress and mitochondrial impairment associated with A beta(1-42) exposure. These results suggest that Oxo could potentially be a novel multi-target drug for treating AD.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2023)
Article
Physiology
Giuditta Gambino, Giuseppe Giglia, Daniele Gallo, Miriana Scordino, Costanza Giardina, Mariachiara Zuccarini, Patrizia Di Iorio, Patricia Giuliani, Francisco Ciruela, Giuseppe Ferraro, Giuseppa Mudo, Pierangelo Sardo, Valentina Di Liberto
Summary: This study investigated the effects of Guanosine (GUO) on the bioelectric activity of human neuroblastoma cells. The results showed that GUO specifically modulated K+-dependent outward currents and its effects were potentiated by adenosine (ADO) receptors. This research provides insights into the role of GUO as a neuromodulator and its interaction with adenosinergic signaling.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Roberta Garozzo, Mariachiara Zuccarini, Patricia Giuliani, Valentina Di Liberto, Giuseppa Mudo, Francesco Caciagli, Renata Ciccarelli, Francisco Ciruela, Patrizia Di Iorio, Daniele F. F. Condorelli
Summary: This study reveals that guanine-based purines inhibit the growth of glioma cells through the modulation of GPR23 receptor. Silencing of GPR23 weakens the antiproliferative effects of guanine-based purines, while cells expressing GPR23 are more sensitive to guanine. The expression of GPR23 is associated with the sensitivity to guanine-based purines in two different cell types, and guanine may exert its effects by binding to GPR23.
FRONTIERS IN PHARMACOLOGY
(2022)