Oligoadenylic Acid Research Articles

Construction of energy transfer pathways self-assembled from DNA-templated stacks of anthracene

We describe optical properties of anthracene stacks formed from single-component self-assembly of thymidylic acid-appended anthracene 2,6-bis[5-(3′-thymidylic acid)pentyloxy] anthracene (TACT) and the binary self-assembly of TACT and complementary 20-meric oligoadenylic acid (TACT/dA20) in an aqueous buffer. UV–Vis and emission spectra for the single-component self-assembly of TACT and the binary self-assembly of TACT/dA20 were very consistent with stacked acene moieties in both self-assemblies. Interestingly, time-resolved fluorescence spectra from anthracene stacks exhibited very different features of the single-component and binary self-assemblies. In the single-component self-assembly of TACT, a dynamic Stokes shift (DSS) and relatively short fluorescence lifetime (τ=0.35ns) observed at around 450nm suggested that the anthracene moieties were flexible. Moreover, a broad emission at 530nm suggested the formation of an excited dimer (excimer). In the binary self-assembly of TACT/dA20, we detected a broad, red-shifted emission component at 534nm with a lifetime (τ=0.4ns) shorter than that observed in the TACT single-component self-assembly. Combining these results with the emission spectrum of the binary self-assembly of TACT/5′-HEX dA20, we concluded that the energy transfer pathway was constructed by columnar anthracene stacks formed from the DNA-templated self-assembly of TACT.

Effects of oligoDNA template length and sequence on binary self-assembly of a nucleotide bolaamphiphile

Templated self-assembly of nucleotide bolaamphiphile 1 (in which a 3'-phosphorylated thymidine moiety is connected to each end of a long oligomethylene chain) with a 10-, 20-, 30-, or 40-meric single-stranded oligoadenylic acid (2, 3, 4, or 5) led to the formation of right-handed helical nanofibers in 0.1x Tris/EDTA (TE) buffer solutions. The helical pitch increased as the length of the oligoadenylic acid template increased. DNA composed of oligoadenylic and oligocytidylic acid sequences (6, 7, and 8) also acted as templates to induce the formation of helical nanofiber structures. The diameter of the nanofibers remained constant (6-6.6 nm) irrespective of the template used. The binary self-assembly of 1 with 4 also produced higher-order, double-stranded nanofibers.

Oligonucleotide-templated self-assembly of nucleotide bolaamphiphiles: DNA-like nanofibers edged by a double-helical arrangement of A-T base pairs.

A stack with a twist is formed when a thymidine bolaamphiphile (green rod with red ends in the scheme) is allowed to interact with strands of oligoadenylic acid (purple chain with yellow pentagons) in aqueous solution. Complementary A–T hydrogen bonding leads to nanofibers having a DNA-like double helix.

Дія 2,5-триолігоаденілату та його епоксипохідного на репродукцію вірусу імунодефіциту людини та на активність зворотної транскриптази ретровірусів

Дія 2,5-триолігоаденілату та його епоксипохідного на репродукцію вірусу імунодефіциту людини та на активність зворотної транскриптази ретровірусів

Противірусна активність тримера 2', 5-олігоаденіловоі кислоти та деяких її аналогів

Противірусна активність тримера 2', 5-олігоаденіловоі кислоти та деяких її аналогів

Renal hemodynamic effects of exogenously administered adenosine and polyadenylic acid.

Steady-state intrarenal arterial infusion of adenosine (Ado) suggests that there may be both afferent and efferent arteriolar actions of Ado. This study attempts to further differentiate vascular sites of action of Ado during an intrarenal infusion of Ado. We measured the filtration fraction (FF) during intrarenal infusion of Ado (33.3 nmol.kg-1 x min-1) in anesthetized dogs to determine its transient actions on renal hemodynamics. FF remained unchanged from preinfusion levels (0.42 +/- 0.01 vs. 0.46 +/- 0.01, respectively) at a time when renal blood flow (RBF) was significantly decreased (52 +/- 6% of control). During steady state, RBF was 96 +/- 5% of control, while FF was significantly decreased from control (0.27 +/- 0.02). To determine whether vasoconstriction and dilation to Ado are mediated by receptors accessible from intra- or extravascular compartments, two Ado analogues [oligoadenylic acid (oligo[A]), mol wt 5,000, and polyadenylic acid (poly[A]), mol wt > 100,000] were injected into the renal artery, and RBF response was compared with that of Ado. Poly[A] produced a transient vasodilation (42 +/- 6% increase in RBF), whereas oligo[A] produced a transient vasoconstriction (25 +/- 5% decrease in RBF). Responses to steady-state infusion of poly[A] (10 nmol.kg-1 x min-1) were determined in 11 anesthetized sodium-depleted dogs. Poly[A] produced a sustained significant increase in RBF from 2.83 +/- 0.31 to 3.92 +/- 0.40 ml.g-1 x min-1. This decrease in renal vascular resistance was blocked by an intrarenal infusion of the Ado antagonist theophylline (0.5 mumol.kg-1 x min-1, 2.68 +/- 0.38 vs. 2.85 +/- 0.38 ml.g-1 x min-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Prompt hydrolysis of oligo(adenylic acid) by poly(vinylamine)

Prompt hydrolysis of oligo(adenylic acid) by poly(vinylamine)

The interactions of Mg2+ and Ni2+ with several oligo-adenylic acids: Equilibria and kinetics

Equilibria and kinetics of the binding of Mg 2+ and Ni 2+ to the oligo-adenylic acids ( Ap) 2 A, ( Ap) 7 A, and ( Ap) 11 A have been investigated at 25°C, ionic strength I ≈ 0.5 M. The equilibria were studied by means of UV spectrophotometric titrations. The observed changes in absorbancy are consistent with those expected for a 1:1 biding stoichiometry. Only for Ni 2+ + ( Ap) 11 A the spectral data are fitted somewhat better with the assumption of a stepwise binding of two Ni 2+ ions to one ligand molecule. The kinetics of the binding processes were studied by applying the temperature-jump relaxation technique. Measurable relaxation effects could not be detected for the systems Mg 2+ + L (L = ligand), apparently indicating that the Mg 2+ is bound predominantly by electrostatic forces (i.e., outer-sphere) to these oligonucleotides under our conditions. By contrast, relaxation effects in the ms range were observed with Ni 2+ + L. The concentration dependence of the time constants can be described by a two-step mechanism in which the first step is assigned to the fast outer-sphere association, with outer-sphere stability constants K 0 equal to those found for the binding of Mg 2+. Again, in the case of Ni 2+ + ( Ap) 11 A the kinetic data can be described better by a mechanism which involves the stepwise binding of 2 Ni 2+ ions. However, only one of the two relaxation times expected for such a process is observed (the longer one). The results of this study are discussed together with the data for several closely related systems.

ChemInform Abstract: Nucleotides. Part 24. Preparative Synthesis of Trimeric (2′‐5′)Oligoadenylic Acid.

ChemInformVolume 18, Issue 45 Natural Products ChemInform Abstract: Nucleotides. Part 24. Preparative Synthesis of Trimeric (2′-5′)Oligoadenylic Acid. E. I. KVASYUK, E. I. KVASYUK CNR, Dip. Chim. Org., Univ. Padova, I-35131 Padova, ItalySearch for more papers by this authorT. I. KULAK, T. I. KULAK CNR, Dip. Chim. Org., Univ. Padova, I-35131 Padova, ItalySearch for more papers by this authorN. B. KHRIPACH, N. B. KHRIPACH CNR, Dip. Chim. Org., Univ. Padova, I-35131 Padova, ItalySearch for more papers by this authorI. A. MIKHAILOPULO, I. A. MIKHAILOPULO CNR, Dip. Chim. Org., Univ. Padova, I-35131 Padova, ItalySearch for more papers by this authorE. UHLMANN, E. UHLMANN CNR, Dip. Chim. Org., Univ. Padova, I-35131 Padova, ItalySearch for more papers by this authorR. CHARUBALA, R. CHARUBALA CNR, Dip. Chim. Org., Univ. Padova, I-35131 Padova, ItalySearch for more papers by this authorW. PFLEIDERER, W. PFLEIDERER CNR, Dip. Chim. Org., Univ. Padova, I-35131 Padova, ItalySearch for more papers by this author E. I. KVASYUK, E. I. KVASYUK CNR, Dip. Chim. Org., Univ. Padova, I-35131 Padova, ItalySearch for more papers by this authorT. I. KULAK, T. I. KULAK CNR, Dip. Chim. Org., Univ. Padova, I-35131 Padova, ItalySearch for more papers by this authorN. B. KHRIPACH, N. B. KHRIPACH CNR, Dip. Chim. Org., Univ. Padova, I-35131 Padova, ItalySearch for more papers by this authorI. A. MIKHAILOPULO, I. A. MIKHAILOPULO CNR, Dip. Chim. Org., Univ. Padova, I-35131 Padova, ItalySearch for more papers by this authorE. UHLMANN, E. UHLMANN CNR, Dip. Chim. Org., Univ. Padova, I-35131 Padova, ItalySearch for more papers by this authorR. CHARUBALA, R. CHARUBALA CNR, Dip. Chim. Org., Univ. Padova, I-35131 Padova, ItalySearch for more papers by this authorW. PFLEIDERER, W. PFLEIDERER CNR, Dip. Chim. Org., Univ. Padova, I-35131 Padova, ItalySearch for more papers by this author First published: November 10, 1987 https://doi.org/10.1002/chin.198745346AboutPDF 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 onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume18, Issue45November 10, 1987 RelatedInformation

Search for catalytic properties of simple polypeptides.

Simple polypeptides were used as possible supports for nucleotide polymerization, in the absence of any preformed polynucleotide template. Sequential copolymers of alanine and glycine, water soluble polypeptides based on arginine and poly(Glu-Ser-Glu) have been tested. No catalytic effect has been found although poly(Glu-Ser-Glu) favors the 2'-5' internucleotide linkage. More interestingly, polypeptides containing arginine residues strongly accelerate the hydrolysis of oligoadenylic acids. The influence of pH, temperature, nature of the buffer and polypeptide sequence was investigated.

Nucleotides XXIV;1Preparative Synthesis of Trimeric (2′-5′) Oligoadenylic Acid

Nucleotides XXIV;¹Preparative Synthesis of Trimeric (2′-5′) Oligoadenylic Acid

70] Methods for the synthesis of analogs of (2′-5′)-oligoadenylic acid

Publisher Summary This chapter discusses, by means of specific examples, several different approaches, found useful in laboratory, to prepare 2-5A analogs. These methods include modification of preformed 2-5A molecules, enzymatic phosphorylation of a “core” oligonucleotide, and lead ion-catalyzed polymerization of 5'-phosphoroimidazolidates of selected nucleosides. The first method described in the chapter for the preparation of analogs of 2-5A, chemical modification of a preformed 2-5A, represents a facile and efficient route, which, in the given example, generates a 2-5A analog that is a significantly more potent inhibitor of protein synthesis and viral replication than the parent 2-5A molecule. The second method detailed in the chapter, T 4 polynucleotide kinase catalyzed phosphorylation of “core” oligonucleotides, is a critical means of obtaining the intermediate oligonucleotide 5'-monophosphate used for the preparation of the corresponding 5'-triphosphates. The last method discussed, lead ion-catalyzed polymerization of a nucleoside 5'-phosphoroimidazolidate as developed originally by Sawai and Ohno, is an extremely valuable technique to obtain the reasonable yields of (2'-5')-linked oligonucleotide 5'-monophosphate in a very short time.

Synthesis and properties of 2',5'-adenylate trimers bearing 2'-terminal 8-bromo- or 8-hydroxyadenosine.

Trimers of 2', 5'-oligoadenylic acids bearing 2'-terminal 8-bromo- or 8-hydroxyadenosine have been synthesized by the phosphotriester method. Some properties of these compounds were studied by circular dichroism (CD) spectroscopy. The 2', 5'-adenylate trimer, A2'p5'A2'p5'HOA (10a) was found to have a less stacked structure than the 2', 5'-adenylate trimers A2'p5'A2'p5'BrA (11) and A2'p5'A2'p5'A (10b).

ChemInform Abstract: SYNTHESIS AND PROPERTIES OF OLIGOADENYLIC ACIDS CONTAINING 2′‐5′ PHOSPHORAMIDE LINKAGE

Chemischer InformationsdienstVolume 15, Issue 46 Natural Products ChemInform Abstract: SYNTHESIS AND PROPERTIES OF OLIGOADENYLIC ACIDS CONTAINING 2′-5′ PHOSPHORAMIDE LINKAGE H. SAWAI, H. SAWAISearch for more papers by this author H. SAWAI, H. SAWAISearch for more papers by this author First published: November 13, 1984 https://doi.org/10.1002/chin.198446351AboutPDF 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 onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume15, Issue46November 13, 1984 RelatedInformation

Synthesis of a modified 2′, 5′-Adenylate trimer with a 2′,3′-Di-O-(2-Carboxyethyl)-ethylidene terminal group

The trimer of 2′, 5′-oligoadenylic acid with a (2-carboxyethyl)ethylidene group ({=1}{=6}) at the 2′-terminal adenosine moiety and its 3′-deoxyadenosine analog ({=1}{=7}) have been synthesized by the phosphotriester method.

ORGANOPHOSPHORUS COMPOUNDS AS ANTIVIRAL AGENTS

Abstract The 5′-triphosphates of 2′-5′ linked oligoadenylic acids are formed in cells which have been exposed to interferon and may be involved in the antiviral activity of the latter. The lead(II) ion-catalysed oligomerisation of adenosine 5′-phosphorimidazolidate is a convenient route for the preparation of the 5′-phosphates of 2′-5′ linked oligoadenylic acids. The latter can readily be converted to the triphosphates or coupled to the 5′-phosphate of nicotinamide nucleoside to give naturally occurring pyrophosphates which may act as reservoirs for the oligoadenylic acids in cells. Pyrophosphate analogues, eg, phosphonoacetic and phosphonoformic acids or carbon-substituted methylenebisphosphonic acids are antiviral agents of potential commercial interest as they inhibit the replication of a number of viruses including herpes and influenza. These pyrophosphate analogues do not appear to inhibit virus replication by being incorporated into nucleoside triphosphates which block nucleic acid synthesis. Rather the analogues appear to act by forming stable complexes with an essential metal ion (probably zinc) at the active sites of nucleic acid polymerases of viruses.

Regulation of the antiviral and anticellular activities of interferon by exogenous double-stranded RNA.

The effects of double-stranded RNA (dsRNA) on interferon (IFN)-induced antiviral and anticellular activities was investigated by introducing poly(I)-poly(C) into mouse L-cells. Coprecipitation of dsRNA with calcium phosphate enabled its efficient penetration into cells in culture. Rate of cellular protein synthesis was inhibited by dsRNA only in cultures pretreated with IFN. Moreover, the anticellular effect of IFN, as measured by the inhibition of cell DNA synthesis, was also enhanced by dsRNA. The kinetics of dsRNA-mediated inhibition of protein synthesis were relatively slow as compared with the inhibitory effect of 2'-5' oligoadenylic acid (2'5'A), which was also introduced into cells by the calcium phosphate coprecipitation technique. To analyze the effects of dsRNA on the antiviral state induced by IFN, vesicular stomatitis virus (VSV) and encephalomyocarditis virus (EMC), replications were followed by measuring viral-specific RNA synthesis in the cell. Introduction of dsRNA after the infection had no effect on VSV and EMC replication in control cells, and it enhanced, to a small extent, the antiviral state of cells pretreated with IFN. In contrast, introduction of 2'5'A into virus-infected cells inhibited VSV and EMC replications regardless of IFN pretreatment. This work demonstrated that the role of dsRNA in regulating the antiviral and anticellular activities of IFN could be studied by introducing exogenous dsRNA into cells in culture by the calcium phosphate coprecipitation technique.

Characterization of antibody to 2'-5' linked oligoadenylic acid.

Antibody to 2'-5' linked triadenylate, A2'p5'A2'p5'A, was prepared by injecting bovine serum albumin conjugated with A2'p5'A2'p5'A into rabbits. The [8-14C]-A2'p5'A2'p5'A used in the study was synthesized by nonenzymatic template-directed condensation of [8-14C]AMP and 5'-phosphorimidazolide of A2'p5'A on poly U. The specificity of the antibody was determined by the inhibition of the binding of the radioisotope probe to the antibody by a competitor using the ammonium sulfate precipitation method. The cross reactivity of a number of modified oligonucleotides has been evaluated in order to gain information on the structural feature involved in the binding to the antibody. The adenine moiety and 2'-5' internucleotide linkage are crucial regions for the binding. The antibody reacted not only on A2'p5'A2'p5'A and A2'p5'A2'p5'A2'p5'A, but also on a cordycepin analogue of the trimer, (3'dA)2'p5'(3'dA)2'p5'(3'dA), significantly. Considerable cross reaction was observed with oligoadenylates bearing both 2'-5' and 3'-5' internucleotide linkages, while there was little cross reaction with 3'-5' linked oligoadenylates. The antibody showed very low or no affinity for adenosine, adenine mononucleotides, other nucleotides and other 2'-5' linked trinucleotides. The cross reactivity of the modified oligonucleotides is indicated to have relation to the biological activity of the corresponding 5'-phosphorylated oligonucleotides, so far reported. The antibody was further purified by affinity chromatography using RNA-Sepharose and AMP-Sepharose giving high specificity.

Structural requirements of (2'-5') oligoadenylate for protein synthesis inhibition in human fibroblasts.

The structural requirements of (2'-5')-oligoadenylic acid (pppA(2'p5'A)x, X greater than or equal to 1 or (2'-5'An) for inhibition of protein synthesis in cells were examined with a modified calcium-coprecipitation technique, using a series of trinucleotide analogs (pppA2'p5'A2'p5'N, N=rC, rG, rU, T, dC, dG, dA). In this system both the degree and the duration of the inhibition of protein synthesis were dependent on the added concentration of (2'-5')A3. Of all the heterotrimers, only the deoxy A derivative was active as an inhibitor of protein synthesis, while the other members of the analog series were found to have no inhibitory effects. In competition experiments between (2'-5')A3 and the non-active analogs, three heterotrimers were shown to reduce the activity of (2'-5')A3 in protein inhibition. In contrast, the dephosphorylated (2'-5')A3 had no inhibitory effect and was not effective in blocking (2'-5')A3. These results indicate that the 5'-terminal triphosphate is important for binding of (2'-5')A3 to the site of (2'-5')An action and the adenine base at the 2'-terminus is important for activating the machinery responsible for protein synthesis inhibition in the cells, most likely the (2'-5')An-activated nuclease.

500 MHz 1H NMR study of the role of lysines and arginines in the binding of gene-5 protein to oligoadenylic acids

500 MHz 1H NMR study of the role of lysines and arginines in the binding of gene-5 protein to oligoadenylic acids