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Nucleosides, Nucleotides & Nucleic Acids 2022has been reported unable to directly incorporate mononucleotides but instead requires their external dephosphorylation by nucleotidases to the corresponding nucleosides...
has been reported unable to directly incorporate mononucleotides but instead requires their external dephosphorylation by nucleotidases to the corresponding nucleosides prior to their incorporation. Although PA-3 (PA-3), a strain of lactic acid bacteria, has been found to incorporate purine mononucleotides such as adenosine 5'-monophosphate (AMP), it remains unclear whether these bacteria directly incorporate these mononucleotides or incorporate them after dephosphorylation to the corresponding nucleosides. This study evaluated whether PA-3 incorporated radioactively-labeled mononucleotides in the presence or absence of the 5'-nucleotidase inhibitor α,β-methylene ADP (APCP). PA-3 took up C-AMP in the presence of APCP, as well as incorporating P-AMP. Furthermore, radioactivity was detected in the RNA/DNA of bacterial cells cultured in the presence of P-AMP. Taken together, these findings indicated that PA-3 incorporated purine mononucleotides directly rather than after their dephosphorylation to purine nucleosides and that PA-3 utilizes these purine mononucleotides in the synthesis of RNA and DNA. Although additional studies are required to identify purine mononucleotide transporters in PA-3, this study is the first to show that some lactic acid bacteria directly incorporate purine mononucleotides and use them for growth.
Topics: Adenosine Monophosphate; Lactobacillus gasseri; Nucleotidases; Purine Nucleosides
PubMed: 32954967
DOI: 10.1080/15257770.2020.1815768 -
Biopolymers Jan 2021The notion of using synthetic heterocycles instead of the native bases to interface with DNA and RNA has been explored for nearly 60 years. Unnatural bases compatible... (Review)
Review
The notion of using synthetic heterocycles instead of the native bases to interface with DNA and RNA has been explored for nearly 60 years. Unnatural bases compatible with the DNA/RNA coding interface have the potential to expand the genetic code and co-opt the machinery of biology to access new macromolecular function; accordingly, this body of research is core to synthetic biology. While much of the literature on artificial bases focuses on code expansion, there is a significant and growing effort on docking synthetic heterocycles to noncoding nucleic acid interfaces; this approach seeks to illuminate major processes of nucleic acids, including regulation of transcription, translation, transport, and transcript lifetimes. These major avenues of research at the coding and noncoding interfaces have in common fundamental principles in molecular recognition. Herein, we provide an overview of foundational literature in biophysics of base recognition and unnatural bases in coding to provide context for the developing area of targeting noncoding nucleic acid interfaces with synthetic bases, with a focus on systems developed through iterative design and biophysical study.
Topics: Base Pairing; DNA; Hydrogen Bonding; Purine Nucleosides; Pyrimidine Nucleosides; RNA; Synthetic Biology
PubMed: 32969496
DOI: 10.1002/bip.23399 -
Molecules (Basel, Switzerland) Mar 2015Transition metal-catalyzed modifications of the activated heterocyclic bases of nucleosides as well as DNA or RNA fragments employing traditional cross-coupling methods... (Review)
Review
Transition metal-catalyzed modifications of the activated heterocyclic bases of nucleosides as well as DNA or RNA fragments employing traditional cross-coupling methods have been well-established in nucleic acid chemistry. This review covers advances in the area of cross-coupling reactions in which nucleosides are functionalized via direct activation of the C8-H bond in purine and the C5-H or C6-H bond in uracil bases. The review focuses on Pd/Cu-catalyzed couplings between unactivated nucleoside bases with aryl halides. It also discusses cross-dehydrogenative arylations and alkenylations as well as other reactions used for modification of nucleoside bases that avoid the use of organometallic precursors and involve direct C-H bond activation in at least one substrate. The scope and efficiency of these coupling reactions along with some mechanistic considerations are discussed.
Topics: Carbon; Catalysis; Hydrogen; Purine Nucleosides; Pyrimidine Nucleosides
PubMed: 25789821
DOI: 10.3390/molecules20034874 -
Journal of the American Chemical Society Oct 2022A new approach for synthesizing polycyclic heterofused 7-deazapurine heterocycles and the corresponding nucleosides was developed based on C-H functionalization of...
A new approach for synthesizing polycyclic heterofused 7-deazapurine heterocycles and the corresponding nucleosides was developed based on C-H functionalization of diverse (hetero)aromatics with dibenzothiophene--oxide followed by the Negishi cross-cooupling with bis(4,6-dichloropyrimidin-5-yl)zinc. This cross-coupling afforded a series of (het)aryl-pyrimidines that were converted to fused deazapurine heterocycles through azidation and thermal cyclization. The fused heterocycles were glycosylated to the corresponding 2'-deoxy- and ribonucleosides, and a series of derivatives were prepared by nucleophilic substitutions at position 4. Four series of new polycyclic thieno-fused 7-deazapurine nucleosides were synthesized using this strategy. Most of the deoxyribonucleosides showed good cytotoxic activity, especially for the CCRF-CEM cell line. Phenyl- and thienyl-substituted thieno-fused 7-deazapurine nucleosides were fluorescent, and the former one was converted to 2'-deoxyribonucleoside triphosphate for enzymatic synthesis of labeled oligonucleotides.
Topics: Nucleosides; Cell Line, Tumor; Ribonucleosides; Pyrimidines; Oxides; Zinc; Oligonucleotides; Deoxyribonucleosides; Purine Nucleosides
PubMed: 36245092
DOI: 10.1021/jacs.2c07517 -
Chemical Society Reviews Jun 2016Supramolecular or molecular gels are attractive for various applications, including diagnostics, tissue scaffolding and targeted drug release. Gelators derived from... (Review)
Review
Supramolecular or molecular gels are attractive for various applications, including diagnostics, tissue scaffolding and targeted drug release. Gelators derived from natural products are of particular interest for biomedical purposes, as they are generally biocompatible and stimuli-responsive. The building blocks of nucleic acids (i.e. nucleobases, nucleosides, and nucleotides) are desirable candidates for supramolecular gelation as they readily engage in reversible, noncovalent interactions. In this review, we describe a number of organo- and hydrogels formed through the assembly of nucleosides, nucleotides, and their derivatives. While natural nucleosides and nucleotides generally require derivatization to induce gelation, guanosine and its corresponding nucleotides are well known gelators. This unique gelating ability is due to propensity of the guanine nucleobase to self-associate into stable higher-order assemblies, such as G-ribbons, G4-quartets, and G-quadruplexes.
Topics: Animals; Drug Stability; Humans; Hydrogels; Nucleotides; Purine Nucleosides; Pyrimidine Nucleosides
PubMed: 27146863
DOI: 10.1039/c6cs00183a -
Advances in Biological Regulation Jan 2023Reversible N6-methyladenosine (mA) RNA modification is a posttranscriptional epigenetic modification of the RNA that regulates many key aspects of RNA metabolism and... (Review)
Review
Reversible N6-methyladenosine (mA) RNA modification is a posttranscriptional epigenetic modification of the RNA that regulates many key aspects of RNA metabolism and function. In this review, we highlight major recent advances in the field, with special emphasis on the potential link between mA modifications and RNA structure. We will also discuss the role of RNA methylation of neuronal transcripts, and the emerging evidence of a potential role in RNA transport and local translation in dendrites and axons of transcripts involved in synaptic functions and axon growth.
Topics: Humans; Methylation; RNA, Messenger; Epigenesis, Genetic; Adenosine; Protein Processing, Post-Translational
PubMed: 36513580
DOI: 10.1016/j.jbior.2022.100926 -
European Journal of Medicinal Chemistry Apr 2021Kinetoplastid parasites are the causative agents of neglected tropical diseases with an unmet medical need. These parasites are unable to synthesize the purine ring de...
Kinetoplastid parasites are the causative agents of neglected tropical diseases with an unmet medical need. These parasites are unable to synthesize the purine ring de novo, and therefore rely on purine salvage to meet their purine demand. Evaluating purine nucleoside analogs is therefore an attractive strategy to identify antikinetoplastid agents. Several anti-Trypanosoma cruzi and anti-Trypanosoma brucei 7-deazapurine nucleosides were previously discovered, with the removal of the 3'-hydroxyl group resulting in a significant boost in activity. In this work we therefore decided to assess the effect of the introduction of a 3'-fluoro substituent in 7-deazapurine nucleosides on the anti-kinetoplastid activities. Hence, we synthesized two series of 3'-deoxy-3'-fluororibofuranosyl and 3'-deoxy-3'-fluoroxylofuranosyl nucleosides comprising 7-deazaadenine and -hypoxanthine bases and assayed these for antiparasitic activity. Several analogs with potent activity against T. cruzi and T. brucei were discovered, indicating that a fluorine atom in the 3'-position is a promising modification for the discovery of antiparasitic nucleosides.
Topics: Cell Line; Cell Survival; Humans; Purine Nucleosides; Purines; Structure-Activity Relationship; Trypanocidal Agents; Trypanosoma brucei brucei; Trypanosoma cruzi
PubMed: 33667845
DOI: 10.1016/j.ejmech.2021.113290 -
Chemistry (Weinheim An Der Bergstrasse,... Jul 2022The prebiotic origins of biopolymers and metabolic co-factors are key questions in Origins of Life studies. In a simple warm-little-pond model, using a drying phase to...
The prebiotic origins of biopolymers and metabolic co-factors are key questions in Origins of Life studies. In a simple warm-little-pond model, using a drying phase to produce a urea-enriched solution, we present a prebiotic synthetic path for the simultaneous formation of neopterins and tetrahydroneopterins, along with purine nucleosides. We show that, in the presence of ribose and in a formylating environment consisting of urea, ammonium formate, and water (UAFW), the formation of neopterins from pyrimidine precursors is robust, while the simultaneous formation of guanosine requires a significantly higher ribose concentration. Furthermore, these reactions provide a tetrahydropterin-pterin redox pair. This model suggests a prebiotic link in the origin of purine nucleosides and pterin cofactors that provides a possible deep prebiotic temporal connection for the emergence of nucleic acids and metabolic cofactors.
Topics: Guanine; Neopterin; Nucleosides; Purine Nucleosides; Pyrimidines; Ribose; Urea
PubMed: 35537135
DOI: 10.1002/chem.202200714 -
Catheterization and Cardiovascular... Jan 2018Chronic total occlusion (CTO) is associated with worse outcomes compared to non CTO percutaneous coronary intervention (PCI). CTO might be associated with vasomotor...
Chronic total occlusion (CTO) is associated with worse outcomes compared to non CTO percutaneous coronary intervention (PCI). CTO might be associated with vasomotor dysfunction Ticagrelor is a novel P2Y12 inhibitor that increases local adenosine The TIGER-BVS trial plans to assess the impact of using ticagrelor vs. clopidogrel on vasomotor activity and outcomes after successful CTO PCI.
Topics: Absorbable Implants; Adenosine; Blood Platelets; Percutaneous Coronary Intervention; Ticagrelor
PubMed: 29314641
DOI: 10.1002/ccd.27456 -
Nucleosides, Nucleotides & Nucleic Acids 2020Dietary purine restrictions are recommended for patients with hyperuricemia and gout. While measuring the purine contents of various foods in our laboratory using...
Measurement of the total purine contents and free nucleosides, nucleotides, and purine bases composition in Japanese anchovies () using high-performance liquid chromatography with UV detection.
Dietary purine restrictions are recommended for patients with hyperuricemia and gout. While measuring the purine contents of various foods in our laboratory using high-performance liquid chromatography (HPLC), we observed and reported changes in purine composition. In this study, we measured the total purine content and free purine of raw anchovies as well as after fermentation, using two methods by HPLC. Method 1 involved acid hydrolysis of all purines, such as nucleic acids and nucleotides, to form four corresponding purine bases. Method 2, which is a non-hydrolysis method, is used to measure the amount of free purines (nucleotide, nucleoside, purine base). As a result of method 1, after fermentation, adenine-related and hypoxanthine-related purines and the total purine levels decreased significantly. Regardless of being raw or fermented, each anchovy contained mainly hypoxanthine- and guanine-related purines. Among the hypoxanthine-related purines, the results of method 2 revealed that the raw anchovies contained a lot of inosine monophosphate (IMP), while after fermentation contained more inosine. In guanine-related and adenine-related purines, those nucleotides decreased by fermentation and nucleosides and bases increased. Measurements of free purines revealed that those reductions after fermentation observed in method 1 were derived from decreased nucleotides. These results indicate that purines are affected by the fermentation bacteria and period.
Topics: Animals; Chromatography, High Pressure Liquid; Fermentation; Fishes; Food Analysis; Purine Nucleosides; Purine Nucleotides; Seafood; Spectrophotometry, Ultraviolet
PubMed: 33231138
DOI: 10.1080/15257770.2020.1809674