Guanine Acid Research Articles

Methylation of ESR1 promoter induced by SNAI2-DNMT3B complex promotes epithelial-mesenchymal transition and correlates with poor prognosis in ERα-positive breast cancers.

Estrogen receptor α (ERα) serves as an essential therapeutic predictor for breast cancer (BC) patients and is regulated by epigenetic modification. Abnormal methylation of cytosine phosphoric acid guanine islands in the estrogen receptor 1 (ESR1) gene promoter could silence or decrease ERα expression. In ERα-negative BC, we previously found snail family transcriptional repressor 2 (SNAI2), a zinc-finger transcriptional factor, recruited lysine-specific demethylase 1 to the promoter to transcriptionally suppress ERα expression by demethylating histone H3 lysine 4 dimethylation (H3K4me2). However, the role of SNAI2 in ERα-positive BC remains elusive. In this study, we observed a positive correlation between SNAI2 and ESR1 methylation, and SNAI2 promoted ESR1 methylation by recruiting DNA methyltransferase 3 beta (DNMT3B) rather than DNA methyltransferase 1 (DNMT1) in ERα-positive BC cells. Subsequent enrichment analysis illustrated that ESR1 methylation is strongly correlated with cell adhesion and junction. Knocking down DNMT3B could partially reverse SNAI2 overexpression-induced cell proliferation, migration, and invasion. Moreover, high DNMT3B expression predicted poor relapse-free survival and overall survival in ERα-positive BC patients. In conclusion, this study demonstrated the novel mechanisms of the ESR1 methylation mediated with the SNAI2/DNMT3B complex and enhanced awareness of ESR1 methylation's role in promoting epithelial-mesenchymal transition in BC.

Antioxidant, Antimicrobial and Spectroscopic Discussion of Guanine Azo Ligand with Cu(II) and Ag (I) Complexes

In this paper, we have provided a very thorough analysis of a new novel chelate metal ion complex of [Cu(II),Ag(I)] prepared via the interaction with the ligand{ 2-amino-8-((4-chloro-3-hydroxyphenyl) diazenyl)azo]guanine} [LAAG], which is synthesized by diazo coupling of the 5-amino-2-chlorophenol with amino acid guanine. The ligand and its complexes are identified by a variety of techniques, like [HNMR, FTIR, and Uv-vis] spectral, thermal analysis (TGA), and element analyses (CHN). The molar ratio was achieved so that the Cu(II) complex has (1:2) (M:L) with octahedral geometry; however, the Ag(I) complex has (1:1) (M:L) with tetrahedral geometry, and the ligand acts as neutral N,N-bidentate; as well as the ligand (LAAG) and its complexes were assessed against the two types of bacteria (Klebsiella pneumonia, Staphylococcus aureus,antifungal (Candida), and antioxidant This study showed that all compounds (the ligand and its complexes) had antimicrobial activity and more biological activity.

Porphyrin‐Based Design of Bioinspired Multitarget Quadruplex Ligands

Secondary nucleic acid structures, such as DNA and RNA quadruplexes, are potential targets for cancer therapies. Ligands that interact with these targets could thus find application as anticancer agents. Synthetic G-quartets have recently found numerous applications, including use as bioinspired G-quadruplex ligands. Herein, the design, synthesis and preliminary biophysical evaluation of a new prototype multitarget G-quadruplex ligand, (PNA)PorphySQ, are reported, where peptidic nucleic acid guanine ((PNA)G) was incorporated in the porphyrin-templated synthetic G-quartet (PorphySQ). Using fluorescence resonance energy transfer (FRET)-melting experiments, PorphySQ was shown to possess enhanced quadruplex-interacting properties thanks to the presence of four positively charged (PNA)G residues that improve its electrostatic interactions with the binding site of both DNA and RNA quadruplexes (i.e., their negatively charged and accessible G-quartets), thereby making (PNA)PorphySQ an interesting prototype of a multitarget ligand. Both the chemical stability and water solubility of (PNA)PorphySQ are improved over the non-PNA derivative (PorphySQ), which are desirable properties for drug development, and while improvements remain to be made, this ligand is a promising lead for the further development of multitarget G-quadruplex ligands.

Liquid Phase Synthesis of Peptide Nucleic Acid (or Polyamide Nucleic Acid) Dimers

The liquid phase synthesis of “polyamide nucleic acid” (PNA) dimers containing the purine nucleic acid bases adenine and guanine has been achieved in good yields. This strategy was elaborated in order to circumvent difficult direct coupling of protected PNA monomers. This method can be applied to the liquid phase synthesis of short protected polyPNAs fragments, which can then selectively be deprotected.

Study of localized levels in proflavine complexes with nucleic acid bases

The semiconduction activation energies of the nucleic acid bases adenine, guanine, thymine and uracil complexes with proflavine dye at various dye concentrations are measured in both the ohmic and the space-charge-limited (SCL) regions. The complexes are found to be nonextrinsic at high dye concentration but approach the extrinsic situation as the dye concentration decreases. From the SCL data analysis various transport parameters are evaluated.

Assignment of resonances of exchangeable protons in the NMR spectrum of the complex formed by Escherichia coli ribosomal protein L25 and uniformly nitrogen-15 enriched 5 S RNA fragment

The downfield proton NMR spectrum of the aqueous nucleoprotein complex formed by Escherichia coli ribosomal protein L25 and uniformly nitrogen-15 enriched 5 S RNA fragment is presented. Many proton resonances show the effects of scalar coupling to nitrogen-15 and these resonances arc assigned to nucleic acid imino protons. Selective nitrogen-15 decoupling difference proton spectroscopy revealed nitrogen-15 and proton chemical shift correlations from which the base types of nucleic acid imino proton resonances could be assigned because the nitrogen-15 chemical shifts of nucleic acid guanine and uracil imino nitrogens have separate small ranges for both nucleoproteins and isolated nucleic acids.

Assignment of resonances in the Escherichia coli 5 S RNA fragment proton NMR spectrum using uniform nitrogen-15 enrichment

The downfield proton NMR spectrum of aqueous uniformly nitrogen-15 enriched 5 S RNA fragment is presented. Selective nitrogen-15 decoupling difference proton spectroscopy revealed nitrogen-15 chemical shifts of fragment imino nitrogens. Nitrogen chemical shifts of nucleic acid guanine and uracil imino nitrogens have separate small ranges. Nitrogen-15 and proton chemical shift correlation by the heteronuclear decoupling permitted the identification of the base type of some previously unassigned imino proton resonances in the 5 S RNA fragment spectrum. Corresponding resonances in the natural isotopic abundance 5 S RNA fragment spectrum are assigned to base types by comparison with the enriched sample spectrum. 5 S RNA fragment Proton NMR Uniform 15N enrichment Heteronuclear decoupling Chemical shift correlation Assignment strategy

Transfer ribonucleic acid guanine transglycosylase isolated from rat liver.

Transfer ribonucleic acid (tRNA) guanine transglycosylase (guanine insertion enzyme) was isolated from rat liver and extensively purified. The enzyme catalyzes an exchange of queuine (the base of queuosine, Q) as well as its precursors and guanine for guanine originally located in the first position of the anticodon of "undermodified" tRNATyr, tRNAHis, tRNAAsn, and tRNAAsp from an Escherichia coli mutant or rat ascites hepatoma cells. This is in contrast to the previous observation that E. coli tRNA-guanine transglycosylase catalyzes the exchange of queuine precursors, such as 7-(aminoethyl)-7-deazaguanine and 7-cyano-7-deazaguanine, but not of queuine itself [Okada, N., Noguchi, S. Kasai, H., Shindo-Okada, N., Ohgi, T., Goto, T., & Nishimura, S. (1979) J. Biol. Chem. 254, 3067-3073]. The Km value for queuine of the rat liver enzyme is 9.2 X 10(-7) M, much lower than the values for the bases of queuosine precursors or guanine. Thus, the actual substrate for tRNA-guanine transglycosylase in queuosine biosynthesis in vivo in rat liver may not be 7-(aminomethyl)-7-deazaguanine, which is thought to be an actual substrate guanine, the E. coli system. Queuine or some queuine derivative may be the actual substrate for the tRNA-guanine transglycosylase reaction in the biosynthesis of Q in tRNA of mammalian cells. 6-Thioguanine and 8-azaguanine are also found to be good substrates.

Metabolism of adenosine in larvae of Drosophila melanogaster

1. 1. Methods have been developed for the study of the metabolism of radioactive adenosine in intact, growing larvae of Drosophila melanogaster. 2. 2. Deamination of ingested adenosine was a major route of metabolism, and some of the inosine so formed was converted to other catabolites. 3. 3. Appreciable amounts of adenosine were converted to adenine nucleotides and to nucleic acid adenine, whereas smaller amounts were converted to inosinate, xanthylate, guanine nucleotides and nucleic acid guanine.

Study of nucleic acid bases by the DADI method

The DADI spectra of the nucleic acid bases adenine (I), guanine (II), Uracil (III), thymine (IV), cytosine (V), and 5-methylcytosine (VI) have been studied. It has been established that the samples of nucleic acid bases investigated are characterized by a specific pattern of the DADI spectra which reflects the nature of the molecular ion due to the structure of the given base and, in the case of M+ for (IV) and (VI) also the tautomeric state. The possibility has been shown of using the information obtained for the quantitative determination of (VI) in a mixture of bases.

Proposal to Elevate the Subspecies of Streptococcus mutans to Species Status, Based on Their Molecular Composition

It is proposed to confer species rank to the genetically distinct streptococci that have been considered subspecies of Streptococcus mutans Clarke: S. mutans subsp. rattus Coykendall, S. mutans subsp. cricetus Coykendall, and S. mutans subsp. sobrinus Coykendall. S. mutans is defined to exclude phenotypically similar bacteria that have deoxyribonucleic acid (DNA) guanine plus cytosine contents appreciably different from 36 to 38 mol% and/or that do not demonstrate DNA base-sequence homology with the type strain. Streptococci that resemble S. mutans but that are quite disparate in molecular constitution are here regarded as comprising four new species: S. rattus (Coykendall) comb. nov., S. cricetus (Coykendall) comb. nov., S. sobrinus (Coykendall) comb. nov., and S. ferus sp. nov. NCTC 10449 is here designated as the neotype strain of S. mutans. The type strains of S. rattus, S. cricetus, S. sobrinus, and S. ferus are FA1 (= ATCC 19645), HS6 (= ATCC 19642), SL1, and 8S1, respectively. Simple biochemical tests serve to identify most strains of all five species. Serological procedures are capable of differentiating most human isolates.

Utilization of dietary nucleic acid purines for nucleotide and nucleic acid synthesis in the mouse.

Three preparations of radioactive yeast nucleic acids were fed to mice. One was labeled predominantly in the guanine moiety, one was labeled predominantly in the adenine moiety, and in one adenine and guanine were labeled equally. Most of the nucleic acid purines produced by digestion were excreted in the urine. However, a small amount was utilized for nucleotide and nucleic acid synthesis in the mouse tissues. Small intestine, liver and skeletal muscle contained most of the purines that were retained in the tissues. Dietary nucleic acid adenine appeared to be utilized somewhat more efficiently than was dietary nucleic acid guanine.

ChemInform Abstract: TAUTOMERISM OF NUCLEIC ACID BASES, GUANINE AND CYTOSINE

Chemischer InformationsdienstVolume 4, Issue 31 Physical Organic Chemistry ChemInform Abstract: TAUTOMERISM OF NUCLEIC ACID BASES, GUANINE AND CYTOSINE YENG P. WONG, YENG P. WONGSearch for more papers by this author YENG P. WONG, YENG P. WONGSearch for more papers by this author First published: July 31, 1973 https://doi.org/10.1002/chin.197331100Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume4, Issue31July 31, 1973 RelatedInformation

N-Hydroxy-2-fluorenylacetamide: REACTION OF THE CARCINOGEN WITH GUANOSINE, RIBONUCLEIC ACID, DEOXYRIBONUCLEIC ACID, AND PROTEIN FOLLOWING ENZYMATIC DEACETYLATION OR ESTERIFICATION

Abstract Previous studies showed that the carcinogen N-hydroxy-2-fluorenylacetamide could react with RNA following enzymatic activation of the hydroxamic acid by deacetylation or esterification. Present studies indicate that 2'-(3')-GMP, but not 2'-(3')-AMP, -CMP, or -UMP, competes effectively with RNA in these reactions. 8-(N-2-Fluorenylamino)-guanosine was isolated and identified after incubation of guanosine, N-hydroxy-2-fluorenylacetamide, and soluble rat liver enzymes in a system favoring deacetylation. This adduct is also formed from reaction of N-2-fluorenylhydroxylamine and guanosine at pH 7.4. 2-Nitrosofluorene, an oxidation product of the hydroxylamine, does not participate in formation of the adduct. 8-(N-2-Fluorenylacetamido)guanosine was recovered following incubation of guanosine, N-hydroxy-2-fluorenylacetamide, rat liver-soluble enzymes, and 3'-phosphoadenosine 5'-phosphosulfate or ATP and MgCl2. The 5'-mononucleotide analogues of the guanosine adducts were identified after nucleic acid modified by reaction with enzymatically activated derivatives of N-hydroxy-2-fluorenylacetamide was treated with phosphodiesterase. Digestion of the nucleotide adducts with alkaline phosphatase yielded the guanosine adducts. These data, considered with results of the competition studies, implicate carbon 8 of nucleic acid guanine as the predominant site of adduct formation. Generation of the enzymatically activated derivatives of N-hydroxy-2-fluorenylacetamide in the presence of DNA or protein results in the incorporation of the carcinogen into these macromolecules. The isolation of 8-(N-2-fluorenylamino)guanosine and 8-(N-2-fluorenylacetamido)guanosine from aqueous solutions by adsorption onto Sephadex G-10 and elution with ethanol is detailed. A nondestructive method for the determination of the specific activity of labeled nucleic acids as their cetyltrimethylammonium salts is described.

Alterations in purine nucleotide biosynthesis induced by 2-amino-6-chloropurine

Exposure of sarcoma 180 ascites cells to 2-amino-6-chloropurine (6-C1G) in vivo resulted in several metabolic lesions in the pathways of purine nucleotide biosynthesis. Pronounced inhibition of the incorporation of glycine-2- 14C into the guanine and adenine nucleotides of the nucleic acids, coupled with blockade of the utilization of 4-amino-5-imidazolecarboxamide-2- 14C solely for the formation of guanine nucleotides, indicated the presence of a site of inhibition on the pathway of purine nucleotide formation de novo. The conversion of hypoxanthine-8- 14C to nucleic acid guanine was markedly decreased by 6-CIG, whereas the utilization of this labeled precursor for the formation of nucleic acid adenine was not lowered by this agent. Under these conditions neither the incorporation of xanthine-8- 14C nor of guanine-8- 14C into the guanine moiety of the nucleic acids was depressed, indicating that 6-CIG or a derivative thereof inhibited the conversion of inosine 5′-phosphate to xanthosine 5′-phosphate. Blockade of this site was confirmed by the finding that 2-amino-6-chloropurine ribonucleoside 5′-phosphate inhibited the activity of inosine 5′-phosphate dehydrogenase. Molar equivalent levels of 2-amino-6-chloropurine ribonucleoside and 2-amino-6-chloropurine ribonucleoside triacetate caused a degree of inhibition of the conversion of hypoxanthine-8- 14C to guanine nucleotides comparable to that produced by 6-C1G. 2-Amino-6-iodopurine ribonucleoside was at least as active an inhibitor of the formation of nucleic acid guanine as the chloro-derivatives.

Metabolism of leptospires. II. The action of 8-azaguanine.

Both the pathogen Leptospira pomona and the saprophyte L. biflexa Patoc I can convert exogenous adenine, guanine, and 8-azaguanine to the corresponding nucleotide and incorporate them into nucleic acids. L. pomona is inhibited by low concentrations of 8-azaguanine (50 μg/ml) and this inhibition is associated with less than a 5% replacement of the ribonucleic acid (RNA) guanine residues by the analogue. Guanine possessed the highest activity for antagonizing the inhibitory effect of 8-azaguanine. The biosynthetic process of L. pomona most affected by the analogue was a relative increase in RNA synthesis. The analogue-resistant L. biflexa incorporated 1/10 as much 8-azaguanine as L. pomona. The higher rate of purine biosynthesis, in addition to the lesser amount of 8-azaguanine incorporated, may account for the analogue resistance of L. biflexa.

Evidence for the Function of P1, P4-Diguanosine 5'-Tetraphosphate in the Development of Artemia salina

Acid extracts of cysts and newly hatched nauplii of Artemia salina contain large amounts of guanine derivatives but only very small amounts of adenine compounds. As the nauplii undergo further differentiation, the total purine concentration remains constant, but the total adenine concentration increases. The increase in total adenine equals the decrease in total guanine. Since the nauplii are incapable of synthesizing purines de novo, a direct conversion of guanine compounds to adenine compounds must occur. Furthermore, P1,P4-diguanosine 5'-tetraphosphate appears to serve as a direct precursor of adenosine triphosphate, its guanine moiety being converted to adenine and its pyrophosphate bonds being conserved in the transition. The other guanine-containing compounds of the acid-soluble pool appear to serve as a source of nucleic acid guanine.

Mutagenicity of cytosine for an adenine and arginine requiring strain of Candida albicans.

An adenine-arginine double auxotroph ofCandida albicans exhibits increased back mutation to arginine independence when cultivated in the presence of growth inhibiting levels of cytosine. Of the natural nucleic acid bases, only adenine or guanine relieve growth inhibition and mutation; adenine is more effective than guanine in relieving inhibition but less effective than guanine in preventing mutation. Previous studies have shown that cytosine renders adenine auxotrophs ofC. albicans purine deficient by competitively interfering with their utilization of exogenous adenine. The mutagenic effect of cytosine reported here is attributed to a cytosine induced cellular deficiency for guanine which favors the erroneous incorporation into replicating DNA of other nucleotides in place of the guanine nucleotide.

Modifications in purine metabolism induced by 6-chloropurine

The effect of 6-chloropurine on the utilization of isotopic precursors of polynucleotide purines was investigated in Sarcoma 180 ascites cells in vivo. Exposure to a dose of the antimetabolite resulted in a marked inhibition of the utilization of glycine-2-C 14 for nucleic acid guanine formation which persisted up to 6 hr. after the drug. Incorporation of glycine into adenine was not decreased. Hypoxanthine-8-C 14 conversion to polynucleotide guanine was unaffected when the isotopic substrate was administered 5 min. after the injection of drug; at later times, slight inhibition of incorporation was found. Utilization of hypoxanthine-C 14 for adenine nucleotide synthesis appeared to be increased. Metabolism of guanine-8-C 14 and adenine-8-C 14 to nucleic acid guanine was stimulated by chloropurine. These findings were suggestive of a compensatory reaction, whereby the cells utilized preformed purines for polynucleotide guanine formation during a period of decreased de novo synthesis of guanine. Possible chloropurine-blocked reaction sites are discussed on the basis of current knowledge concerning purine biosynthesis.

Effects of 8-azaguanine on the synthesis of protein and nucleic acids in Bacillus cereus.

THE guanine analogue, 8-azaguanine, inhibits growth of a variety of tissues and micro-organisms, possibly as a result of its incorporation into ribo-nucleic acids. In Bacillus cereus, as much as 40 per cent of the ribonucleic acid guanine has been shown to be replaced by azaguanine1. The inhibition of growth of these bacteria (as estimated from optical density measurements) conceals more complex changes of metabolism, especially a dissociation of the formation of ribonucleic acid from that of protein2. These changes have now been more thoroughly studied, and the essential observations are the subject of this communication.