70062-83-8Relevant academic research and scientific papers
Natural occurrence of 2′,5′-linked heteronucleotides in marine sponges
Lopp, Annika,Reintamm, Tonu,Kuusksalu, Anne,Tammiste, Indrek,Pihlak, Arno,Kelve, Merike
experimental part, p. 235 - 254 (2010/10/19)
2′,5′-oligoadenylate synthetases (OAS) as a component of mammalian interferon-induced antiviral enzymatic system catalyze the oligomerization of cellular ATP into 2′,5′-linked oligoadenylates (2-5A). Though vertebrate OASs have been characterized as 2′-nucleotidyl transferases under in vitro conditions, the natural occurrence of 2′,5′-oligonucleotides other than 2-5A has never been demonstrated. Here we have demonstrated that OASs from the marine sponges Thenea muricata and Chondrilla nucula are able to catalyze in vivo synthesis of 2-5A as well as the synthesis of a series 2′,5′-linked heteronucleotides which accompanied high levels of 2′,5′-diadenylates. In dephosphorylated perchloric acid extracts of the sponges, these heteronucleotides were identified as A2′p5′G, A2′p5′U, A2′p5′C, G2′p5′A and G2′p5′U. The natural occurrence of 2′-adenylated NAD+ was also detected. In vitro assays demonstrated that besides ATP, GTP was a good substrate for the sponge OAS, especially for OAS from C. nucula. Pyrimidine nucleotides UTP and CTP were also used as substrates for oligomerization, giving 2′,5′-linked homo-oligomers. These data refer to the substrate specificity of sponge OASs that is remarkably different from that of vertebrate OASs. Further studies of OASs from sponges may help to elucidate evolutionary and functional aspects of OASs as proteins of the nucleotidyltransferase family.
High yield synthesis, purification and characterisation of the RNase L activators 5'-triphosphate 2′-5′-oligoadenylates
Morin,Rabah,Boretto-Soler,Tolou,Alvarez,Canard
experimental part, p. 345 - 352 (2011/10/07)
Upon viral infection, double-stranded viral RNA is detected very early in the host cell by several cellular 2′-5′ oligoadenylate synthetases, which synthesize 2′-5′ adenylate oligonucleotides that activate the cellular RNase L, firing an early primary antiviral response through self and non-self RNA cleavage. Transfecting cells with synthetic 2′-5′ adenylate oligonucleotides activate RNase L, and thus provide a useful shortcut to study the early steps of cellular and viral commitments into this pathway. Defined 2′-5′ adenylate oligonucleotides can be produced in vitro, but their controlled synthesis, purification, and characterisation have not been reported in detail. Here, we report a method suitable to produce large amounts of 2-5As of defined lengths in vitro using porcine OAS1 (pOAS) and human OAS2 (hOAS). We have synthesized a broad spectrum of 2-5As at the milligram scale and report an HPLC-purification and characterisation protocol with quantified yield for 2-5A of various lengths.
Acid/azole complexes as highly effective promoters in the synthesis of DNA and RNA oligomers via the phosphoramidite method
Hayakawa,Kawai,Hirata,Sugimoto,Kataoka,Sakakura,Hirose,Noyori
, p. 8165 - 8176 (2007/10/03)
The utility of various kinds of acid salts of azole derivatives as promoters for the condensation of a nucleoside phosphoramidite and a nucleoside is investigated. Among the salts, N-(phenyl)imidazolium triflate, N-(p-acetylphenyl)imidazolium triflate, N-
Synthesis of 1'%,2',3',4'%,5',5"-(2)H6-β-D-ribonucleosides and 1'%,2',2",3',4'%,5',5"-(2)H7-β-D-2'-deoxyribonucleosides for Selective Suppression of Proton Resonances in Partially-deuterated Oligo-DNA, Oligo-RNA and in 2,5A core ((1)H-NMR window)
Foeldesi, Andras,Nilson, Frans Peder R.,Glemarec, Corine,Gioeli, Carlo,Chattopadhyaya, Jyoti
, p. 9033 - 9072 (2007/10/02)
Raney nickel-(2)H2O exchange reaction on an epimeric mixture of methyl α/β-D-ribofuranoside 1 produced methyl 1%,2,3,4%,5,5'-(2)H6-α/β-D-ribofuranoside 2 ( >97 atom percent (2)H at C2, C3, C5/5'; ca. 85 atom percent (2)H at C4(C4%); ca. 20 atom percent (2)H at C1(C1%)) which was obtained in 60 - 80percent yield along with epimeric xylo and arabino by-products.Toluoylation of the crude 2 in dry pyridine and a careful separation on a column of silica gel gave pure 1-O-methyl-2,3,5-tri-O-(4-toluoyl)-α/β-D-1%,2,3,4%,5,5'-(2)H6-ribofuranoside 4 (48percent).Conversion of 4 to1-O-acetyl-2,3,5-tri-O-toluoyl-α/β-D-1%,2,3,4%,5,5'-(2)H6-ribofuranoside 6 (82percent) provided the crucial building block for the synthesis of deuterionucleosides for RNA or DNA synthesis.Compound 6 was then condensed with silyated uracil, N4-benzoylcytosine, N6-benzoyladenine, N2-acetyl-O6-diphenylcarbamoylguanine and thymine in anhydrous solvent using trimethylsilyl trifluoromethanesulfonate to give the corresponding isomerically pure 1'%,2',3',4'%,5',5"-(2)H6-ribonucleoside derivatives 7, 8, 9, 10, 11 in 75, 85, 60, 73 and 91percent yields, respectively. 1'%,2',3',4'%,5',5"-(2)H6-ribonucleosides 13-16 were converted in high yields to the corresponding 1'%,2',2",3',4'%,5',5"-(2)H7-2'-deoxynucleosides 41-44 in the following manner: 3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl (TPDS)-1'%,2',3',4'%,5',5"-(2)H6-nucleosides 29-32 were converted to the corresponding 2'-O-phenoxythiocarbonyl derivatives 33-36, which were deoxygenated by tri-n-butyltin deuteride to give 1'%,2',2",3',4'%,5',5"-(2)H7-2'-deoxynucleosides 37-40 and subsequently deprotected to give 41-44.Pure 1'%,2',3',4'%,5',5"-(2)H6-ribonucleoside derivatives 12-15, 1'%,2',2",3',4'%,5',5"-(2)H7-2'-deoxynucleoside blocks 41-44 and their natural-abundance counterparts were then used to assemble partially deuterated ribonucleotide-dimers (* indicates deuterated moiety): UpA* 77, CpG* 78, ApU* 79, GpC* 80, partially deuterated 2'-deoxyribonucleotide-dimers d(TpA*) 93, d(CpG*) 94, d(ApT*) 95, d(GpC*) 96 and partially deuterated 2,5A core (A*2'p5'A2'p5'A*) (109).These nine partially deuterated oligonucleotides were subsequently compared with their corresponding natural-abundance counterparts by 500 MHz (1)H-NMR spectroscopy to evaluate the actual NMR simplifications achieved in the non-deuterated part ((1)H-NMR window) as a result of specific deuterium incorporation.Detailed 1D (1)H-NMR (500 MHz), 2D correlation spectra (DQF-COSY and TOCSY), T1 measurements for (1)H-, (13)C- and INEPT (13)C-NMR spectra have been presented and discussed to assess the utility of stereospecific deuterium incorporation to create the (1)H- or (13)C-NMR window.
SYNTHESIS OF 2'-END LIPOPHILIZED DERIVATIVES OF 2',5'-TRIADENYLATES
Pressova, Martina,Smrt, Jiri
, p. 487 - 497 (2007/10/02)
Synthesis of protected derivatives of 2 - 5 A3 core starting from 2',3'-O-ethoxymethylene-N6-benzoyladenosine (I) by triazolidate and/or modified triester method are described.Preparation of adenylyl-(2'-5')-adenylyl-(2'-5')-2',3'-O-(1-methoxyhexadecylidene)adenosine (X), adenylyl-(2'-5')-adenylyl-(2'-5')-2'(3')-O-palmitoyladenosine (XIII) and 5'-phosphoryladenyl-(2'-5')-adenylyl-(2'-5')-2',3'-O-(1-methoxyhexadecylidene)adenosine (XVI) are described.
Nucleotides XXIV; Preparative Synthesis of Trimeric (2'-5')Oligoadenylic Acid
Kvasyuk, Evgeny I.,Kulak, Tamara I.,Khripach, Natalya B.,Mikhailopulo, Igor A.,Uhlmann, Eugen,et al.
, p. 535 - 541 (2007/10/02)
A preparative synthesis of the 2'-5'-Oligoadenylate trimer 19 via the phosphotriester approach is described.Selectively benzoylated derivatives of adenosine were used as starting materials.
Synthesis and properties of 2',5'-adenylate trimers bearing 2'-terminal 8-bromo or 8-hydroxyadenosine
Yoshida, Shiro,Takaku, Hiroshi
, p. 2456 - 2461 (2007/10/02)
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 less stacked structure than the 2',5'-adenylate trimers A2'p5'A2'p5'BrA (11) and A2'p5'A2'p5'A (10b).Keywords - modified 2',5'-adenylate trimer; N6,N6,3'-O-tribenzoyladenosine; 8-bromoadenosine; coupling agent; CD spectrum; HPLC; reversed-phase liquid chromatography.
Expedient Chemical Synthesis of Sequence-Specific 2',5'-Oligonucleotides
Imai, Jiro,Torrence, Paul F.
, p. 1418 - 1426 (2007/10/02)
A rapid chemical approach to the preparation of sequence-specific 2',5'-oligonucleotides and analogues of 2-5A is described.For instance, reaction of the 5'-phosphoromorpholidate of adenosine (MopA, 14) with the 5'-phosphoroimidazolidate of inosine (ImpI, 17), under conditions of lead ion catalysis, gave MopA2'p5'I (19a) in 21percent yield.Acid hydrolysis of 19a gave pA2'p5'I, which then was converted to the corresponding 5'-phosphoroimidazolidate Imp5'A2'p5'I (19c) through redox condensation with triphenylphosphine, imidazole, and 2,2-dipyridyl disulfide.Lead ion catalyzed condensation of 19c with Mop5'A (14) gave Mop5'A2'p5'A2'p5'I (30) in 17percent yield.By acid hydrolysis, 30 could be converted to the corresponding 5'-monophosphate, or, by reaction with pyrophosphate in DMF, to the corresponding 2-5A analogue, ppp5'A2'p5'A2'p5'I (5b).The following oligonucleotides were prepared by using similar methodology: ppp5'A2'p5'A2'p5'A (1b), ppp5'A2'p5'I2'p5'A (4b), ppp5'I2'p5'A2'p5'A (3b), and ppp5'A2'p5'A2'p5'(2'dA) (2b).
CONVENIENT METHOD FOR THE SYNTHESIS OF ADENYLYL-(2 prime - 5 prime )-ADENYLYL-(2 prime - 5 prime )-ADENOSINE USING 3 prime -O-BENZOYLADENOSINE DERIVATIVES.
Takaku,Ueda
, p. 1424 - 1427 (2007/10/02)
N**6,3 prime -O-Dibenzoyladenosine was prepared by treating 2 prime ,3 prime -0-(dibutylstannylene)-N**6-benzolyladenosine with benzoyl chloride in methanol. The trimeric adenylyl-(2 prime - 5 prime k)-adenylyl-(2 prime - 5 prime )-adenosine was synthesized in a good yield using N**6,3 prime - O-dibenzoyladenosine as the starting material via the phosphotriester approach.
