- Role of the stereochemistry of 3'-fluoro-3'-deoxy analogues of 2-5A in binding to and activation of mouse RNase L
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The synthesis of two sets of analogues of 2-5A trimer containing 9-(3-fluoro-3-deoxy-β-D-xylo-furanosyl)adenine (AF) or 3'-fluoro-3'-deoxyadenosine (AF) at different positions of the chain is described, along with the preparation of the corresponding 5'-monophosphates and 5'-diphosphorylated (core) trimers.The ability of each ribo and xylo isomeric pair of fluorodeoxy analogues of 2-5A (i) to compete with p3(A2'p)3A3'pC3'p for binding to RNase L in L929 cell extracts, and (ii) to activate the partially purified RNase L from L929 cell extracts to hydrolyze poly(U), was compared to that of the related 3'-deoxy analogue and the parent trimer, p3A3, using radiobinding and RNase L-(2',5')pentaadenylate(core)-agarose assays, respectively.Evidence is presented to show that the stereochemistry of the trimers plays an important role, specifically in the second process.The most striking observation is that, compared to 2-5A, p3A(AF)A was found to be nine times more effective an activator of RNase L, whereas isomeric p3A(AF)A is 30 times less effective.
- Kalinichenko, Elena N.,Podkopaeva, Tatjana L.,Poopeiko, Nicolai E.,Kelve, Merike,Saarma, Mart,et al.
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- Uranyl Ion as a Highly Effective Catalyst for Internucleotide Bond Formation
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Uranyl ion catalyzes the polymerization of adenosine-5'-phosphorimidazolide very efficiently in aqueous solution.Up to 95percent of the imput adenosine-5'-phosphorimidazolide is converted to oligoadenilates from dimer to hexadecamer when 1mM of UO(2+) is used as a catalyst.The oligomeric products are predominantly 2'-5' linked.The chain length and the regioselectivity of the resulting oligoadenylates varies greatly with the concentration of the UO(2+) ion catalyst and the pH of the reaction medium.A high total yield of oligouridyllates up to dodecamer is also obtained by UO(2+) ion catalyst with high 2'-5' regioselectivity.The oligonucleotide formation is mediated by UO(2+)-nucleotide complex.
- Sawai, Hiroaki,Kuroda, Kensei,Hojo, Takashi
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p. 2018 - 2023
(2007/10/02)
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- Expedient Chemical Synthesis of Sequence-Specific 2',5'-Oligonucleotides
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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).
- Imai, Jiro,Torrence, Paul F.
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p. 1418 - 1426
(2007/10/02)
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