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Molecular BioSystems Nov 2014The 8-azapurines, and their 7-deaza and 9-deaza congeners, represent a unique class of isosteric (isomorphic) analogues of the natural purines, frequently capable of... (Review)
Review
The 8-azapurines, and their 7-deaza and 9-deaza congeners, represent a unique class of isosteric (isomorphic) analogues of the natural purines, frequently capable of substituting for the latter in many biochemical processes. Particularly interesting is their propensity to exhibit pH-dependent room-temperature fluorescence in aqueous medium, and in non-polar media. We herein review the physico-chemical properties of this class of compounds, with particular emphasis on the fluorescence emission properties of their neutral and/or ionic species, which has led to their widespread use as fluorescent probes in enzymology, including enzymes involved in purine metabolism, agonists/antagonists of adenosine receptors, mechanisms of catalytic RNAs, RNA editing, etc. They are also exceptionally useful fluorescent probes for analytical and clinical applications in crude cell homogenates.
Topics: Enzymes; Fluorescent Dyes; Humans; Models, Molecular; Nucleic Acids; Purine Nucleosides; Purine Nucleotides; Purines; Spectrometry, Fluorescence
PubMed: 25124808
DOI: 10.1039/c4mb00233d -
Molecules (Basel, Switzerland) Apr 2020Nucleoside analogues have proven to be highly successful chemotherapeutic agents in the treatment of a wide variety of cancers. Several such compounds, including... (Review)
Review
Nucleoside analogues have proven to be highly successful chemotherapeutic agents in the treatment of a wide variety of cancers. Several such compounds, including gemcitabine and cytarabine, are the go-to option in first-line treatments. However, these materials do have limitations and the development of next generation compounds remains a topic of significant interest and necessity. Herein, we discuss recent advances in the chemical synthesis and biological evaluation of nucleoside analogues as potential anticancer agents. Focus is paid to 4'-heteroatom substitution of the furanose oxygen, 2'-, 3'-, 4'- and 5'-position ring modifications and the development of new prodrug strategies for these materials.
Topics: Adenosine; Animals; Antineoplastic Agents; Cell Line, Tumor; Drug Design; Drug Screening Assays, Antitumor; Furans; Humans; K562 Cells; Mice; Molecular Structure; Nucleosides; Oxygen; Prodrugs; Purine Nucleosides; Pyrimidinones; Thionucleosides; Vitamin E
PubMed: 32354007
DOI: 10.3390/molecules25092050 -
Cells Jan 2022Inosine triphosphate pyrophosphatase (ITPase) is an enzyme encoded by the gene and functions to prevent the incorporation of noncanonical purine nucleotides into DNA... (Review)
Review
Inosine triphosphate pyrophosphatase (ITPase) is an enzyme encoded by the gene and functions to prevent the incorporation of noncanonical purine nucleotides into DNA and RNA. Specifically, the ITPase catalyzed the hydrolysis of (deoxy) nucleoside triphosphates ((d) NTPs) into the corresponding nucleoside monophosphate with the concomitant release of pyrophosphate. Recently, thiopurine drug metabolites such as azathioprine have been included in the lists of ITPase substrates. Interestingly, inosine or xanthosine triphosphate (ITP/XTP) and their deoxy analogs, deoxy inosine or xanthosine triphosphate (dITP/dXTP), are products of important biological reactions such as deamination that take place within the cellular compartments. However, the incorporation of ITP/XTP, dITP/dXTP, or the genetic deficiency or polymorphism of the gene have been implicated in many human diseases, including infantile epileptic encephalopathy, early onset of tuberculosis, and the responsiveness of patients to cancer therapy. This review provides an up-to-date report on the ITPase enzyme, including information regarding its discovery, analysis, and cellular localization, its implication in human diseases including cancer, and its therapeutic potential, amongst others.
Topics: Humans; Inosine; Inosine Triphosphate; Mutation; Neoplasms; Nucleosides; Nucleotides; Pyrophosphatases; Inosine Triphosphatase
PubMed: 35159194
DOI: 10.3390/cells11030384 -
ACS Nano Nov 2023This work addresses the challenge of delivering bioactive molecules by designing biocompatible nanogel particles (NGPs) utilizing rationally modified nature-sourced...
This work addresses the challenge of delivering bioactive molecules by designing biocompatible nanogel particles (NGPs) utilizing rationally modified nature-sourced building blocks: capryl-oligochitosan and oxidized inosine. Capryl substituents endowed the resultant NGPs with membrane-penetration capabilities, while purine-containing inosine allowed H-bond/π-π/π-cation interactions. The prepared NGPs were complexed with carboxyfluorescein-labeled single-stranded oligonucleotide (FAM-oligo) and DsRed-encoding plasmid DNA. The successful delivery of FAM-oligo to the cell cytoplasm of the plant was observed. Alexa 555-labeled bovine serum albumin (Alexa 555-BSA) was also efficiently encapsulated and delivered to the plant. In addition to delivering FAM-oligo and Alexa 555-BSA separately, NGPs also successfully co-delivered both biomolecules to the plant. Finally, NGPs successfully encapsulated the drug amphotericin B and reduced its toxicity while maintaining its efficacy. The presented findings suggest that NGPs may become a promising platform for the advanced delivery of bioactive molecules in various applications.
Topics: Nanogels; Nucleosides; Oligosaccharides; Inosine; Serum Albumin, Bovine; Drug Delivery Systems
PubMed: 37934119
DOI: 10.1021/acsnano.3c08627 -
Nucleosides, Nucleotides & Nucleic Acids 2021Antimetabolites, which are metabolic antagonists used in the treatment of cancer and viral diseases by replacing metabolites, inhibit the action of metabolic enzymes and...
Antimetabolites, which are metabolic antagonists used in the treatment of cancer and viral diseases by replacing metabolites, inhibit the action of metabolic enzymes and disrupt the pathways of synthesis of structural units necessary for the formation of nucleic acids. Purine antagonists, that are subunits of antimetabolites, reduce the production of purine bases, and hence, cause the nucleotide production to stop and bring about the death of cancer cells. Fludarabine (2-fluoro-ara-AMP), which is used in chemotherapy, is an antimetabolite of the purine class containing mono phosphate in its structure. In this study, a protocol was presented to effectively and efficiently synthesis of 6-(4-phenylpiperazine-1-yl)-9-(β-D-ribofuranosyl)-9-purine-5'- O-phosphate compound in six steps and 25% overall yield starting with commercially available 6-chloropurine.
Topics: Models, Molecular; Molecular Conformation; Phosphorylation; Purine Nucleosides; Stereoisomerism
PubMed: 33416028
DOI: 10.1080/15257770.2020.1843679 -
Current Protocols in Nucleic Acid... Dec 2020The protocols presented in this article describe highly detailed synthesis of trifluoromethylated purine nucleotides and nucleosides (G and A). The procedure involves...
The protocols presented in this article describe highly detailed synthesis of trifluoromethylated purine nucleotides and nucleosides (G and A). The procedure involves trifluoromethylation of properly protected (acetylated) nucleosides, followed by deprotection leading to key CF -containing nucleosides. This gives synthetic access to 8-CF -substituted guanosine derivatives and three adenosine derivatives (8-CF , 2-CF , and 2,8-diCF ). In further steps, phosphorylation and phosphate elongation (for selected examples) result in respective trifluoromethylated nucleoside mono-, di-, and triphosphates. Support protocols are included for compound handling, purification procedures, analytical sample preparation, and analytical techniques used throughout the performance of the basic protocols. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Synthesis of trifluoromethylated guanosine and adenosine derivatives Basic Protocol 2: Synthesis of trifluoromethylated guanosine and adenosine monophosphates Basic Protocol 3: Synthesis of phosphorimidazolides of GMP and AMP Basic Protocol 4: Synthesis of trifluoromethylated guanosine and adenosine oligophosphates Support Protocol 1: TLC sample preparation and analysis Support Protocol 2: Purification protocol for Basic Protocol 1 Support Protocol 3: HPLC analysis and preparative HPLC Support Protocol 4: Ion-exchange chromatography.
Topics: Fluorine; Methylation; Purine Nucleosides; Purines; Ribonucleotides; Spectrum Analysis
PubMed: 32991077
DOI: 10.1002/cpnc.118 -
International Journal of Molecular... Dec 2023Adenosine-to-inosine (A-to-I) RNA editing is the most prevalent RNA modification in the nervous systems of metazoans. To study the biological significance of RNA... (Review)
Review
Adenosine-to-inosine (A-to-I) RNA editing is the most prevalent RNA modification in the nervous systems of metazoans. To study the biological significance of RNA editing, we first have to accurately identify these editing events from the transcriptome. The genome-wide identification of RNA editing sites remains a challenging task. In this review, we will first introduce the occurrence, regulation, and importance of A-to-I RNA editing and then describe the established bioinformatic procedures and difficulties in the accurate identification of these sit esespecially in small sized non-model insects. In brief, (1) to obtain an accurate profile of RNA editing sites, a transcriptome coupled with the DNA resequencing of a matched sample is favorable; (2) the single-cell sequencing technique is ready to be applied to RNA editing studies, but there are a few limitations to overcome; (3) during mapping and variant calling steps, various issues, like mapping and base quality, soft-clipping, and the positions of mismatches on reads, should be carefully considered; (4) Sanger sequencing of both RNA and the matched DNA is the best verification of RNA editing sites, but other auxiliary evidence, like the nonsynonymous-to-synonymous ratio or the linkage information, is also helpful for judging the reliability of editing sites. We have systematically reviewed the understanding of the biological significance of RNA editing and summarized the methodology for identifying such editing events. We also raised several promising aspects and challenges in this field. With insightful perspectives on both scientific and technical issues, our review will benefit the researchers in the broader RNA editing community.
Topics: Transcriptome; RNA; RNA Editing; Reproducibility of Results; Adenosine; DNA; Inosine
PubMed: 38138955
DOI: 10.3390/ijms242417126 -
Advances in Clinical and Experimental... 2017Under homeostatic conditions, an equilibrium state between amounts of free radicals formed and their scavenging is observed. Free radicals are destructive only when... (Review)
Review
Under homeostatic conditions, an equilibrium state between amounts of free radicals formed and their scavenging is observed. Free radicals are destructive only when present in excess. Pathological changes within cells and tissues can result from a persistent excess of free radicals. Living organisms are increasingly exposed to oxidative stress, resulting in oxidative DNA modifications. One such modification is 8-hydroxy-2'-deoxyguanosine (8-OHdG). It is considered a biomarker of oxidative stress and oxidative DNA damage. It has been found both in physiological fluids and in cells. This paper presents methods found in the literature for determining 8-OHdG expression in various kinds of biological material - blood, urine or liver homogenates. Methods for determining the biomarker expression have been grouped into direct and indirect methods, and the various levels of 8-hydroxy-2'-deoxyguanosine that can be determined by the different techniques are presented. The basic pros and cons of the various techniques are also discussed.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Biomarkers; DNA Damage; Deoxyguanosine; Free Radicals; Humans; Oxidative Stress
PubMed: 28397448
DOI: 10.17219/acem/43272 -
Journal of Chromatography. A Aug 2014Improved nitrogen utilization in cattle is important in order to secure a sustainable cattle production. As purines and pyrimidines (PP) constitute an appreciable part...
Simultaneous quantification of purine and pyrimidine bases, nucleosides and their degradation products in bovine blood plasma by high performance liquid chromatography tandem mass spectrometry.
Improved nitrogen utilization in cattle is important in order to secure a sustainable cattle production. As purines and pyrimidines (PP) constitute an appreciable part of rumen nitrogen, an improved understanding of the absorption and intermediary metabolism of PP is essential. The present work describes the development and validation of a sensitive and specific method for simultaneous determination of 20 purines (adenine, guanine, guanosine, inosine, 2'-deoxyguanosine, 2'-deoxyinosine, xanthine, hypoxanthine), pyrimidines (cytosine, thymine, uracil, cytidine, uridine, thymidine, 2'-deoxyuridine), and their degradation products (uric acid, allantoin, β-alanine, β-ureidopropionic acid, β-aminoisobutyric acid) in blood plasma of dairy cows. The high performance liquid chromatography-based technique coupled to electrospray ionization tandem mass spectrometry (LC-MS/MS) was combined with individual matrix-matched calibration standards and stable isotopically labelled reference compounds. The quantitative analysis was preceded by a novel pre-treatment procedure consisting of ethanol precipitation, filtration, evaporation and reconstitution. Parameters for separation and detection during the LC-MS/MS analysis were investigated. It was confirmed that using a log-calibration model rather than a linear calibration model resulted in lower CV% and a lack of fit test demonstrated a satisfying linear regression. The method covers concentration ranges for each metabolite according to that in actual samples, e.g. guanine: 0.10-5.0 μmol/L, and allantoin: 120-500 μmol/L. The CV% for the chosen quantification ranges were below 25%. The method has good repeatability (CV%≤25%) and intermediate precision (CV%≤25%) and excellent recoveries (91-107%). All metabolites demonstrated good long-term stability and good stability within-runs (CV%≤10%). Different degrees of absolute matrix effects were observed in plasma, urine and milk. The determination of relative matrix effects revealed that the method was suitable for almost all examined PP metabolites in plasma drawn from an artery and the portal hepatic, hepatic and gastrosplenic veins and, with a few exceptions, also for other species such as chicken, pig, mink, human and rat.
Topics: Animals; Calibration; Cattle; Chromatography, High Pressure Liquid; Humans; Milk; Mink; Purine Nucleosides; Pyrimidine Nucleosides; Rats; Reference Standards; Spectrometry, Mass, Electrospray Ionization; Swine; Tandem Mass Spectrometry
PubMed: 25017393
DOI: 10.1016/j.chroma.2014.06.065 -
Archives of Cardiovascular Diseases 2016
Review
Topics: Acute Coronary Syndrome; Adenosine; Humans; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome
PubMed: 27342807
DOI: 10.1016/j.acvd.2016.04.001