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)
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.
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)
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
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
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
Yacoba V. T. Minnow, Vern L. Schramm, Steven C. Almo, Agnidipta Ghosh
Summary: Purine nucleoside phosphorylases (PNPs) catalyze the phosphorolysis of 6-oxypurine nucleosides and their HPO42- binding site plays a crucial role in PNP activity and subunit cooperativity. Alterations in the HPO42- binding site can lead to PNP inactivation and affect binding to transition-state analogue inhibitors.
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
Sebastien Alphonse, Ankan Banerjee, Swathi Dantuluri, Stewart Shuman, Ranajeet Ghose
Summary: Tpt1, an essential component of the fungal and plant tRNA splicing machinery, catalyzes transfer of an internal RNA 2'-PO4 to NAD(+) yielding RNA 2'-OH and ADP-ribose-1',2'-cyclic phosphate products. NMR structures of the Tpt1 ortholog from the bacterium Runella slithyformis (RslTpt1) were reported, showing significant inter-lobe dynamics in the free and NAD(+)-bound states. Functional analysis indicated that substrate affinity is primarily determined by the ADP moiety and NAD(+) interacts with specific residues essential for Tpt1 activity.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Sebastien Alphonse, Ankan Banerjee, Swathi Dantuluri, Stewart Shuman, Ranajeet Ghose
Summary: The NMR structures of RsITpt1 in free and NAD(+) bound states reveal substantial inter-lobe dynamics. ITC measurements show that substrate affinity is primarily determined by the ADP moiety. NAD(+)-induced chemical shift perturbations are localized to the C-lobe of RsITpt1.
NUCLEIC ACIDS RESEARCH
(2021)
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
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
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
Biophysics
David L. Bostick, Karunesh Arora, Charles L. Brooks
BIOPHYSICAL JOURNAL
(2009)
Article
Biophysics
Kenji Yoshimoto, Karunesh Arora, Charles L. Brooks
BIOPHYSICAL JOURNAL
(2010)
Article
Biochemistry & Molecular Biology
Benedetta A. Sampoli Benitez, Karunesh Arora, Lisa Balistreri, Tamar Schlick
JOURNAL OF MOLECULAR BIOLOGY
(2008)
Article
Chemistry, Multidisciplinary
Karunesh Arora, Charles L. Brooks
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2009)
Article
Multidisciplinary Sciences
Karunesh Arora, Charles L. Brooks
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2007)
Article
Biochemistry & Molecular Biology
Ravi Radhakrishnan, Karunesh Arora, Yanli Wang, William A. Beard, Samuel H. Wilson, Tamar Schlick
Article
Biophysics
Meredith C. Foley, Karunesh Arora, Tamar Schlick
BIOPHYSICAL JOURNAL
(2006)
Article
Biochemistry & Molecular Biology
K Arora, WA Beard, SH Wilson, T Schlick
Article
Chemistry, Physical
K Arora, T Schlick
JOURNAL OF PHYSICAL CHEMISTRY B
(2005)
Article
Chemistry, Multidisciplinary
H Singh, K Arora, S Tapadar, TK Chakraborty
JOURNAL OF THEORETICAL & COMPUTATIONAL CHEMISTRY
(2004)
Article
Biophysics
K Arora, T Schlick
BIOPHYSICAL JOURNAL
(2004)
Article
Chemistry, Multidisciplinary
LJ Yang, K Arora, WA Beard, SH Wilson, T Schlick
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2004)
Article
Biochemistry & Molecular Biology
YL Wang, K Arora, T Schlick
Article
Biophysics
BAS Benitez, K Arora, T Schlick
BIOPHYSICAL JOURNAL
(2006)