PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Guanosine”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1976

Guanosine tetraphyosphate and its analogues. Chemical synthesis of guanosine 3',5'-dipyrophosphate, deoxyguanosine 3',5'-dipyrophosphate, guanosine 2',5'-bis(methylenediphosphonate), and guanosine 3',5'-bis(methylenediphosphonate).

A new procedure for the synthesis of the pyrophosphate bond has been employed in the preparation of nucleoside dipyrophosphates from nucleoside 3',5'-diphosphates. The method makes use of a powerful phosphorylating agent generated in a mixture of cyanoethyl phosphate, dicyclohexylcarbodiimide, and mesitylenesulfonyl chloride in order to avoid possible intramolecular reactions between the two phosphate groups on the sugar ring. That such reactions can readily occur was shown by the facile cyclization of deoxyguanosine 3',5'-diphosphate to P1,P2-deoxyguanosine 3',5'-cyclic pyrophosphate in the presence of dicyclohexylcarbodiimide alone. The phosphorylation reagent was initially tested in the conversion of deoxyguanosine 3',5'-diphosphate to the corresponding 3',5'-dipyrophosphate and was then used to phosphorylate 2'-O-(alpha-methoxyethyl)guanosine 3',5'-diphosphate, which had been prepared from 2'-O-(alpha-methoxyethyl)guanosine. In the latter case, the addition of the two beta phosphate groups was accomplished in 40% yield. Removal of the methoxyethyl group from the phosphorylated product gave guanosine 3',5'-dipyrophosphate, which was shown to be identical with guanosine tetraphosphate prepared enzymatically from a mixture of GDP and ATP. A modification of published procedures was also necessary to effect the synthesis of guanosine bis(methylenediphosphonate). Guanosine was treated with methylenediphosphonic acid and dicyclohexylcarbodiimide in the absence of added base. The product consisted of a mixture of guanosine 2',5' - and 3',5'-bis(methylenediphosphonate), which was resolved by anion-exchange chromatography. The 2',5' and 3',5' isomers are interconvertible at low pH, with the ultimate formation of an equilibrium mixture having a composition ratio of 2:3. The predominant constituent of this mixture has been unequivocally identified as the 3',5' isomer by synthesis from 2'-O-tetrahydropyranylguanosine.

Alkaline Phosphatase↗
PubMed1978

The presence of guanosine 5'-diphospho-5'-guanosine and guanosine 5'-triphospho-5'-adenosine in brine shrimp embryos.

Acid-soluble extracts of dormant embryos of the brine shrimp, Artemia salina, contain small amounts of two previously undescribed dinucleotides which we have identified to be guanosine 5'-diphospho-5'-guanosine and guanosine 5'-triphospho-5'-adenosine. These compounds each comprise about 0.03% of the dry weight of the encysted embryos and are related chemically to guanosine 5'-triphospho-5'-guanosine and guanosine 5'-tetraphospho-5'-guanosine which have been shown previously to be major constituents of the nucleotide pool of Artemia cysts. These new dinucleotides were purified from perchloric acid extracts of dormant cysts by ion exchange column chromatography and identified by means of chemical, spectrophotometric, and enzymatic analyses compared to commercially available compounds. The possible role of these new compounds in nucleotide and nucleic acid metabolism in Artemia embryos is discussed.

Adenosine↗
PubMed2001

Structure-activity relationships of diadenosine polyphosphates (Ap(n)As), adenosine polyphospho guanosines (Ap(n)Gs) and guanosine polyphospho guanosines (Gp(n)Gs) at P2 receptors in the rat mesenteric arterial bed.

1. Vascular effects of diadenosine polyphosphates (Ap(n)As), adenosine polyphospho guanosines (Ap(n)Gs) and guanosine polyphospho guanosines (Gp(n)Gs), novel families of naturally-occurring signalling molecules, were investigated in methoxamine preconstricted rat isolated perfused mesenteric arterial beds. 2. Three different types of response were elicited by Ap(n)As and Ap(n)Gs. Those with a short polyphosphate chain (n=2 - 3) elicited vasorelaxation. Ap(3)A was more potent than Ap(2)A, and both were more potent than the corresponding Ap(n)G. Relaxations to Ap(3)A and Ap(3)G, but not to Ap(2)A and Ap(2)G, were blocked by endothelium removal and pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), a P2 receptor antagonist. 3. Longer polyphosphate chain Ap(n)As and Ap(n)Gs (n=4 - 6) elicited dose-dependent vasoconstriction followed by prolonged vasorelaxation, with a potency order for both types of response of Ap(5)A> or =Ap(6)A>Ap(4)A. A similar order and potency was observed for Ap(n)Gs. Contractions and prolonged relaxations were blocked by PPADS and P2X(1) receptor desensitization with alpha,beta-methylene ATP (alpha,beta-meATP), and were largely endothelium-independent. 4. In the presence of alpha,beta-meATP rapid relaxations to contractile Ap(n)As and Ap(n)Gs (n=4 - 6) were revealed. 5. Gp(n)Gs were virtually inactive, except for Gp(2)G which elicited vasoconstriction via PPADS- and alpha,beta-meATP-sensitive smooth muscle P2X(1)-like receptors. 6. These data show that, as with Ap(n)As, the length of the polyphosphate chain (n) is an important determinant of the activity of Ap(n)Gs at P2 receptors in the rat mesenteric arterial bed. When the chain is short (n=2 - 3) the purines elicit rapid vasorelaxation, which for Ap(3)A and Ap(3)G is mediated via endothelial P2Y(1)-like receptors. When the chain is long (n=4 - 6) Ap(n)As and Ap(n)Gs elicit vasoconstriction via P2X(1)-like receptors, followed by prolonged endothelium-independent vasorelaxation. Rapid relaxation to contractile dinucleotides (n=4 - 6) is revealed by block of vasoconstriction. Regarding the purine moiety, one adenine is crucial and sufficient for vasoactivity as Gp(n)Gs were largely inactive, and Ap(n)As and Ap(n)Gs approximately equipotent.

Adenosine Triphosphate↗
PubMed1998

Adenosine(5') oligophospho-(5') guanosines and guanosine(5') oligophospho-(5') guanosines in human platelets.

We isolated and identified nucleoside(5') oligophospho-(5') nucleosides containing adenosine and guanosine (ApnG; n = 3-6) as well as diguanosine polyphosphates (GpnG; n = 3-6) in human platelets. For identification, UV spectrometry, matrix-assisted laser desorption/ionization, postsource decay matrix-assisted laser desorption/ionization mass spectrometry, and enzymatic cleavage experiments were used. The adenosine(5') oligophospho-(5') guanosines act as vasoconstrictors and growth factors. The diguanosine polyphosphates are potent modulators of growth in vascular smooth muscle cells, but do not affect vascular tone.

Adenosine↗
PubMed1974

Effects of guanosine tetraphosphate, guanosine pentaphosphate, and beta-gamma methylenyl-guanosine pentaphosphate on gene expression of Escherichia coli in vitro.

The effects of guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp), both produced by E. coli, were measured on the activities of several genes in a cell-free system. Gene activity is measured as gene-directed synthesis of biochemically competent protein or transfer RNA. Both ppGpp and pppGpp stimulated the activities of the ara, lac, and trp operons and inhibited the arg operon. Production of transfer-RNA(Tyr) was unaffected by moderate levels of either ppGpp or pppGpp and only slightly inhibited at higher levels of ppGpp. Since the cell-free reaction mixtures hydrolyze pppGpp to ppGpp, we performed similar studies with a hydrolysis-resistant analog of pppGpp, the beta-gamma methylenyl derivative (pcppGpp). In general, pcppGpp shows the same inhibitory potency as pppGpp for the arg operon, but lacks the stimulatory effects on the ara, lac, and trp operons. This result suggests that the stimulation of these gene activities is specific for ppGpp.Under similar conditions, pppGpp and ppGpp show a slight inhibitory effect on the messenger-directed synthesis of beta-galactosidase and no effect on the messenger-directed synthesis of MS2 viral-coat protein. These observations, together with the fact that in the same system these nucleotides affect coupled transcription and translation, lead us to surmise that the activities of pppGpp and ppGpp are exerted at the level of RNA polymerase activity.

Acetamides↗
PubMed1991

Guanosine metabolism in adult rat cardiac myocytes: ribose-enhanced GTP synthesis from extracellular guanosine.

The metabolic fate of transported guanosine was examined in adult rat cardiac myocytes. Freshly isolated cells were incubated with 10 microM or 100 microM [3H]guanosine and the nucleotide products extracted and examined for radiolabel distribution. The data presented show significant incorporation of guanosine into the 5'-nucleotide pool, and a marked stimulation of that incorporation by ribose. An average of 233 pmol/mg cell protein extracellular guanosine was incorporated into the cellular 5'-nucleotides over 90 min at both 10 microM and 100 microM external nucleoside. This appeared primarily as GTP (approx. 204 pmol/mg cell protein in 90 min). Only guanine nucleotides contained radiolabel; adenine nucleotides and IMP remained unlabelled even after 90 min incubation of the cells with [3H]guanosine. Addition of 5 mM ribose to the medium stimulated guanosine incorporation into 5'-nucleotides 1.6-fold (380 pmol/mg protein vs 234 pmol/mg over 90 min at 10 microM guanosine), but did not enhance the amount of guanosine transported into the cells. Intracellular guanosine concentrations exceeded those of the incubation medium at both external guanosine concentrations studied. More [3H]guanosine was salvaged at 100 microM than at 10 microM external guanosine (562 vs 380 pmol/mg protein in 90 min), but only if ribose was present in the medium. We conclude from these studies that guanosine is salvaged by heart muscle, and that at high guanosine levels the rate of guanosine salvage appears dependent on the availability of phosphoribosylpyrophosphate within the cells. At lower guanosine levels in the presence of ribose, cell guanine concentrations limit the rate of guanosine incorporation into 5'-nucleotides.

Animals↗
PubMed1975

Interaction of guanosine nucleotides with elongation factor 2. II. Effect of ribosomes and magnesium ions on guanosine diphosphate and guanosine triphosphate binding to the enzyme.

The effects of ribosomes and Mg-2plus on the binding of GDP and GTP to elongation factor 2 (EF-2) have been studied by an improved filter-binding assay. Both ribosomes and Mg-2plus strongly inhibit the binding of GDP but have apparently no effect on the GTP binding to the enzyme. An apparent stimulation by ribosomes of GTP binding to EF-2 is time-dependent and parallels a concomitant increase of the GDP concentration in the incubation mixture. Based on these results and evidence obtained by other investigators it is suggested that changes in the GTP:GDP ratio associated with the elongation and termination reactions of protein synthesis cause conformational changes of the respective factors which consequently will modulate the binding and dissociation of the enzymes from ribosomes. Further evidence of the role GDP may play as a modulator of protein synthesis might possibly be provided by studies of the GTP-GDP transphosphorylase activity which is present as an impurity in highly purified preparations of EF-2 as well as in ribosome preparations. It is demonstrated that relatively high concentrations of GDP in the presence of GTP completely block the ribosome-dependent GTPase activity of EF-2. Instead, the transphosphorylase enzyme(s) catalyzes an exchange reaction between GTP and GDP during which GDP remains bound to EF-2 and the relative concentrations of the two nucleotides do not change.

Animals↗
PubMed1991

Evidence for a substrate-binding subsite in ribonuclease T1. Crystal structure of the complex with two guanosines, and model building of the complex with the substrate guanylyl-3',5'-guanosine.

The enzyme ribonuclease T1 cleaves single-stranded RNA at the 3'-side of guanosine. The structure of the complex with two guanosines has been analyzed at 1.8-A resolution and refined to a crystallographic R value of 14.0%. One guanosine occupies the guanosine recognition site as observed in previously analyzed complexes of ribonuclease T1 with guanosine phosphates. The other is bound to a base-unspecific subsite marking the binding locus of the nucleoside 3'-proximal to guanosine in a cleavable RNA chain. The positions of the guanosine bound to the recognition site and of the guanine base at the subsite were used to guide model building of the substrate guanylyl-3',5'-guanosine bound to the active site of ribonuclease T1. After energy minimization and a 7-ps stochastic dynamics simulation, a plausible model of the enzyme-substrate complex was obtained which may serve as a reference point in consideration of the mechanisms of RNA hydrolysis by ribonuclease T1.

Crystallization↗
PubMed1975

Nucleotide specificity of stringent factor and the synthesis of analogs of guanosine 5'-diphosphate 3'-diphosphate and guanosine 5'-triphosphate 3'-diphosphate.

The ribosome-dependent stringent factor reaction was found to be nonspecific with regard to the number of phosphate groups linked to the 5' position of guanosine nucleotides. Both GMP and guanosine 5'-tetraphosphate could accept a pyrophosphoryl group from ATP although at a much lower rate than GDP or GTP. Guanosine 5'-monophosphate 3'-diphosphate and guanosine 5'-tetraphosphate 3'-diphosphate were the products of these reactions. Furthermore, 3'-linked analogs of guanosine 5'-diphosphate 3'-diphosphate and guanosine 5'-triphosphate 3'-diphosphate were synthesized from the corresponding ATP analog, adenosine 5'-O-(3-thiotriphosphate). The stringent factor catalyzed reverse reaction was found to be specific for guanosine 5'-diphosphate 3'-diphosphate, and was essentially inactive to the isomeric form, guanosine 5'-diphosphate 2'-diphosphate.

Bacterial Proteins↗
PubMed1980

Accumulation of guanosine tetraphosphate and guanosine pentaphosphate in Myxococcus xanthus during starvation and myxospore formation.

Cultures of Myxococcus xanthus develop multicellular fruiting bodies when starved for carbon and nitrogen sources on an agar surface. Under these conditions of severe starvation, cultures rapidly accumulated a compound identified as guanosine tetraphosphate by chromatographic migration of the compound and of its major acid and alkali breakdown products. The accumulation of guanosine tetraphosphate was reduced in the presence of tetracycline, indicating that it may be synthesized by mechanisms similar to those of Escherichia coli. The guanosine tetraphosphate level was also reduced in starved cultures of a mutant unable to fruit normally, although it has been determined whether the defect in guanosine tetraphosphate accumulation is responsible for the inability to fruit. Induction of spores by glycerol addition led to transient increases in both guanosine tetraphosphate and guanosine pentaphosphate at a stage following most cell shortening, but before spores had acquired full refractility.

Adenosine Triphosphate↗
PubMed2001

A calorimetric study of 3d metal ions-acyclovir interactions. The 2-hydroxyethoxymethyl group of acyclovir mimics the role of ribose in deoxy-guanosine and guanosine promoting the coordination through N(7).

The equilibrium constants and enthalpic values of metal acyclovir complexes have been determined by calorimetry for Co(II) (log K=0.96+/-0.05, DeltaH (kJ/mol)=-19.7+/-1.3), Ni(II) (log K=1.39+/-0.03, DeltaH (kJ/mol)=-21.5+/-1.0), Cu(II) (log K=1.83+/-0.03, DeltaH (kJ/mol)=-23.2+/-0.8) and Zn(II) (log K=0.71+/-0.06, DeltaH (kJ/mol)=-18.6+/-1.5). The equilibrium constants are similar to those of the divalent ions with guanosine and 2,9-dimethylpurine. By comparison with previous thermodynamic data, it can be shown that the 2-hydroxyethoxymethyl group promotes coordination through N(7) versus N(1) of the guanine ring for 3d metal ions. These results reveal that the 2-hydroxyethoxymethyl group placed on the purine ring of guanine in acyclovir causes a greater effect than that of the 9-methyl in purines and similar to or greater than that of the ribose moiety in guanosine. The 2-hydroxyethyoxymethyl group of acyclovir mimics the role of ribose in deoxy-guanosine and guanosine promoting a similar coordination chemistry (with very close log K and DeltaH values) for acyclovir, deoxy-guanosine and guanosine with divalent metals.

Acyclovir↗
PubMed1989

Role of guanosine kinase in the utilization of guanosine for nucleotide synthesis in Escherichia coli.

Using purine auxotrophic strains of Escherichia coli with additional genetic lesions in the pathways of interconversion and salvage of purine compounds, we demonstrated the in vivo function of guanosine kinase and inosine kinase. Mutants with increased ability to utilize guanosine were isolated by plating cells on medium with guanosine as the sole purine source. These mutants had altered guanosine kinase activity and the mutations were mapped in the gene encoding guanosine kinase, gsk. Some of the mutants had acquired an additional genetic lesion in the purine de novo biosynthetic pathway, namely a purF, a purL or a purM mutation. A revised map location of the gsk gene is presented and the gene order established as proC-acrA-apt-adk-gsk-purE.

Bacterial Proteins↗
PubMedDate not supplied

Efficient methods for the synthesis of [2-15N]guanosine and 2'-deoxy[2-15N]guanosine derivatives.

The nucleophilic addition-elimination reaction of 2',3',5'-tri-O-acetyl-2-fluoro-O6-[2-(4-nitrophenyl)ethyl]inosine (8) with [15N]benzylamine in the presence of triethylamine afforded the N2-benzyl[2-15N]guanosine derivative (13) in a high yield, which was further converted into the N2-benzoyl[2-15N] guanosine derivative by treatment with ruthenium trichloride and tetrabutylammonium periodate. A similar sequence of reactions of 2',3',5'-tri-O-acetyl-2-fluoro-06-[2-(methylthio)ethyl]inosine (9) and the 6-chloro-2-fluoro-9-(beta-D-ribofuranosyl)-9H-purine derivative (11), which were respectively prepared from guanosine, with potassium [15N]phthalimide afforded the N2-phthaloyl [2-15N]guanosine derivative (15; 62%) and 9-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-6-chloro-2-[15N]phthalimido-9H-purine (17; 64%), respectively. Compounds 15 and 17 were then efficiently converted into 2',3',5'-tri-O-acetyl [2-15N]guanosine. The corresponding 2'-deoxy derivatives (16 and 18) were also synthesized through similar procedures.

Chromatography↗
PubMed1982

Synthesis and characterization of diastereomers of guanosine 5'-O-(1-thiotriphosphate) and guanosine 5'-O-(2-thiotriphosphate).

The synthesis and characterization of guanosine 5'-O-(1-thiotriphosphate) (GTP alpha S) and guanosine 5'-O-(2-thiotriphosphate) (GTP beta S) using chemical and enzymatic methods are described. GTP alpha S A (SP diastereomer) can be prepared enzymatically from a chemically synthesized mixture of the diastereomers of guanosine 5'-O-(1-thiodiphosphate) (GDP alpha S) with phosphoglycerate kinase. GTP alpha S B (RP diastereomer) can be similarly synthesized with succinyl-CoA synthetase and by back-digesting the small amounts of GTP alpha S A formed with phosphoglycerate kinase. Guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) serves as the precursor for both GTP beta S A (SP diastereomer), prepared with pyruvate kinase and by back-digesting with glycerol kinase, and GTP beta S B (RP diastereomer), obtained with acetate kinase and by back-digesting with myosin. These analogues can be gamma-32P labeled by 32Pi exchange with either phosphoglycerate kinase-phosphoglyceraldehyde dehydrogenase or succinyl-CoA synthetase. Finally, the interaction of these four nucleotides with acetate kinase, RNA polymerase, and succinyl-CoA synthetase is described.

Acetate Kinase↗