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European Biophysics Journal : EBJ Oct 20238-azaguanine is a triazolopyrimidine nucleobase analog possessing potent antibacterial and antitumor activities, and it has been implicated as a lead molecule in cancer...
8-azaguanine is a triazolopyrimidine nucleobase analog possessing potent antibacterial and antitumor activities, and it has been implicated as a lead molecule in cancer and malaria therapy. Its intrinsic fluorescence properties can be utilized for monitoring its interactions with biological polymers like proteins or nucleic acids. In order to better understand these interactions, it is important to know the tautomeric equilibrium of this compound. In this work, the tautomeric equilibrium of all natural neutral and anionic compound forms (except highly improbable imino-enol tautomers) as well as their methyl derivatives and ribosides was revealed by quantum chemistry methods. It was shown that, as expected, tautomers protonated at positions 1 and 9 dominate neutral forms both in gas phase and in aqueous solution. 8-azaguanines methylated at any position of the triazole ring are protonated at position 1. The computed vertical absorption and emission energies are in very good agreement with the experimental data. They confirm the validity of the assumption that replacing the proton with the methyl group does not significantly change the positions of absorption and fluorescence peaks.
Topics: Azaguanine; Spectrum Analysis; Protons; Proteins; Quantum Theory
PubMed: 37507591
DOI: 10.1007/s00249-023-01672-x -
Cancer Investigation Jun 2012The involvement of apoptosis in the cytotoxicity mediated by nucleoside analogues, namely azaguanine, and its implication in resistance are not well understood. Using...
The involvement of apoptosis in the cytotoxicity mediated by nucleoside analogues, namely azaguanine, and its implication in resistance are not well understood. Using human T-cell acute lymphoblastic leukemia cell lines, sensitive (CEM cells) and resistant to azaguanine (CM3 cells), we observe a decrease in the expression of proapoptotic proteins in CM3 cells, which may be related to the resistance to cell death induced by azaguanine. On the other hand, CM3 cells lack cross resistance with other anticarcinogenic drugs, suggesting that azaguanine may be used alternatively in the presence of chemoresistance. A better knowledge of the apoptotic pathways involved in leukemic cell death resistance may contribute to the development of therapeutic strategies, aimed to prevent chemotherapy resistance.
Topics: Antimetabolites, Antineoplastic; Apoptosis; Azaguanine; Cell Line, Tumor; Drug Resistance, Neoplasm; Humans; Immunophenotyping; Leukemia
PubMed: 22348536
DOI: 10.3109/07357907.2012.659925 -
Journal of the American Chemical Society Mar 2007The fluorescent nucleotide analogue 8-azaguanosine-5'-triphosphate (8azaGTP) is prepared easily by in vitro enzymatic synthesis methods. 8azaGTP is an efficient...
The fluorescent nucleotide analogue 8-azaguanosine-5'-triphosphate (8azaGTP) is prepared easily by in vitro enzymatic synthesis methods. 8azaGTP is an efficient substrate for T7 RNA polymerase and is incorporated specifically opposite cytosine in the transcription template, as expected for a nucleobase analogue with the same Watson-Crick hydrogen bonding face as guanine. 8-Azaguanine (8azaG) in oligonucleotides also is recognized as guanine during ribonuclease T1 digestion. Moreover, replacement of guanine by 8azaG does not alter the melting temperature of base-paired RNAs significantly, evidence that 8azaG does not disrupt stacking and hydrogen bonding interactions. 8azaGTP displays a high fluorescent quantum yield when the N1 position is deprotonated at high pH, but fluorescence intensity decreases significantly when N1 is protonated at neutral pH. Fluorescence is quenched 10-fold to 100-fold when 8azaG is incorporated into base-paired RNA and remains pH-dependent, although apparent pKa values determined from the pH dependence of fluorescence intensity shift in the basic direction. Thus, 8azaG is a guanine analogue that does not perturb RNA structure and displays pH-dependent fluorescence that can be used to probe the ionization states of nucleobases in structured RNAs. A key application will be in determining the ionization state of active site nucleobases that have been implicated in the catalytic mechanisms of RNA enzymes.
Topics: Azaguanine; Base Sequence; Guanosine Triphosphate; Hydrogen-Ion Concentration; Ions; Kinetics; Molecular Sequence Data; RNA; Spectrometry, Fluorescence
PubMed: 17326637
DOI: 10.1021/ja067699e -
Biochimica Et Biophysica Acta Mar 19758-Azaguanine (10- minus 4 M) supplementation in synthetic medium inhibited flavinogenesis in Eremothecium ashbyii to far greater extent (68per cent) than the growth (25...
8-Azaguanine (10- minus 4 M) supplementation in synthetic medium inhibited flavinogenesis in Eremothecium ashbyii to far greater extent (68per cent) than the growth (25 per cent). That enzymes comprising the biosynthetic pathway of riboflavin are synthesized during early growth phase of the organism is supported by the data presented. 8-Azaguanine mediated inhibition in flavinogenesis was closely related with decreased levels of ribose-5'-phosphatase, ribose reductase and ribitol kinase, the enzymes involved in supplying ribitol for flavinogenesis. Addition of guanine and not ribitol during early growth phase to 8-azaguanine-added cultures released the inhibition of riboflavin synthesis and restored the enzyme levels in the presence of the antimetabolite.
Topics: Alcohol Oxidoreductases; Ascomycota; Azaguanine; Depression, Chemical; Dose-Response Relationship, Drug; Guanine; Phosphoric Monoester Hydrolases; Phosphotransferases; Phosphotransferases (Alcohol Group Acceptor); Plants; Protein Biosynthesis; Riboflavin; Ribose; Ribosemonophosphates; Saccharomycetales; Sugar Alcohols
PubMed: 164925
DOI: 10.1016/0304-4165(75)90073-2 -
Spectrochimica Acta. Part A, Molecular... Nov 2003A comparative study, luminescence behavior of 6-Mercaptopurine (6-MP), Azathiopurine (BAN), and 8-Azaguanine (8-Azan) have been investigated including the low...
A comparative study, luminescence behavior of 6-Mercaptopurine (6-MP), Azathiopurine (BAN), and 8-Azaguanine (8-Azan) have been investigated including the low temperature phosphorescence, the low temperature fluorescence, the room temperature phosphorescence (RTP) and the room temperature fluorescence (RTF). The effect of pH on the luminescence intensity is discussed. Analytical characteristics of RTF and RTP of 6-MP, BAN, and 8-Azan have been studied. The lifetime of phosphorescence and the polarity of RTF and RTP have been examined.
Topics: Azaguanine; Hydrogen-Ion Concentration; Luminescence; Mercaptopurine; Spectrometry, Fluorescence; Spectrophotometry
PubMed: 14583288
DOI: 10.1016/s1386-1425(03)00121-5 -
Bioconjugate Chemistry Jul 2018The α-anomers of 8-aza-2'-deoxyguanosine (αG*) and 2'-deoxyguanosine (αG) were site-specifically incorporated in 12-mer duplexes opposite to the four canonical DNA...
The α-anomers of 8-aza-2'-deoxyguanosine (αG*) and 2'-deoxyguanosine (αG) were site-specifically incorporated in 12-mer duplexes opposite to the four canonical DNA constituents dA, dG, dT, and dC. Oligodeoxyribonucleotides containing αG* display significant fluorescence at slightly elevated pH (8.0). Oligodeoxyribonucleotides incorporating β-anomeric 8-aza-2'-deoxyguanosine (G*) and canonical dG were studied for comparison. For αG* synthesis, an efficient purification of anomeric 8-azaguanine nucleosides was developed on the basis of protected intermediates, and a new αG* phosphoramidite was prepared. Differences were observed for sugar conformations ( N vs S) and p K values of anomeric nucleosides. Duplex stability and mismatch discrimination were studied employing UV-dependent melting and fluorescence quenching. A gradual fluorescence change takes place in duplex DNA when the α-nucleoside αG* was positioned opposite to the four canonical β-nucleosides. The strongest fluorescence decrease appeared in duplexes incorporating αG*-C base pair matches. Decreasing fluorescence corresponds to increasing T values. For mismatch discrimination, the α-anomers αG* and αG are more efficient than the corresponding β-nucleosides. Duplexes with single "purine-purine" αG*-αG* or αG-αG base pairs are significantly more stable than those displaying β-d configuration. CD spectra indicate that single mutations by α-anomeric nucleosides do not affect the global structure of B-DNA.
Topics: Azaguanine; Base Pair Mismatch; Base Pairing; DNA, B-Form; Fluorescence; Guanine; Nucleic Acid Conformation; Oligodeoxyribonucleotides; Transition Temperature
PubMed: 29771499
DOI: 10.1021/acs.bioconjchem.8b00261 -
The Journal of Biological Chemistry Nov 1956
Topics: Adenosine Deaminase; Amidohydrolases; Azaguanine; Guanine; Humans; In Vitro Techniques
PubMed: 13376577
DOI: No ID Found -
In Vitro May 1983A clone of Vero cells resistant to up to 20 micrograms/ml 8-azaguanine was isolated. This clone (designated Vero 153) has a doubling rate of approximately 24 h and a...
A clone of Vero cells resistant to up to 20 micrograms/ml 8-azaguanine was isolated. This clone (designated Vero 153) has a doubling rate of approximately 24 h and a maximum cell density of 10,000/mm2. Deficiency of the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT) in Vero 153 was demonstrated by methods of radiochromatography. Vero 153 is susceptible to hypoxanthine-thymidine-aminopterin (HAT) medium and its resistance to 8-azaguanine seems to be nonreversible. Like parental cells, Vero 153 was also incapable of interferon production when challenged with Newcastle disease virus (NDV) or poly(inosinic acid) . poly(cytidylic acid) (poly I:C). Similar chromosome complements (majority range 56 to 57) and band patterns were observed in cells harvested at Passages 10, 20, and 50. The potential use of Vero 153 for somatic cell hybridization for purposes of gene mapping, virus rescue, and the control of interferon production is discussed.
Topics: Aminopterin; Animals; Azaguanine; Cell Line; Cell Separation; Chlorocebus aethiops; Clone Cells; Culture Media; Drug Resistance; Hypoxanthine; Hypoxanthine Phosphoribosyltransferase; Hypoxanthines; Interferons; Karyotyping; Kidney; Mutation; Thymidine
PubMed: 6190732
DOI: 10.1007/BF02619558 -
Nature Feb 1954
Topics: Azaguanine; Guanine; Nucleic Acids
PubMed: 13144756
DOI: 10.1038/173346a0 -
Analytical Biochemistry Oct 1967
Topics: Animals; Azaguanine; Barbiturates; Bicarbonates; Bromine; Buffers; Carbonates; Chemical Phenomena; Chemistry; Colorimetry; Cyanides; Liver; Mice; Nitrogen; Sodium Hydroxide; Spectrophotometry; Xanthines
PubMed: 6062769
DOI: 10.1016/0003-2697(67)90094-2