- Complex and method for enhancing nuclear delivery
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The use of at least one nucleic acid based nuclear localization signal including a natural or synthetic m3G-CAP is shown to increase transmembrane transport of a molecular cargo, in particular large molecules, into the nucleus. The use of natur
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Page/Page column 15
(2015/07/07)
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- METABOLITE BIOMARKERS FOR THE DETECTION OF ESOPHAGEAL CANCER USING MS
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Results of studies of nucleosides in biofluid specimens from patients with esophageal adenocarcinoma and related disorders have identified five biomarkers of the conditions: 1-methyladenosine, N2,N2-dimethylguanosine, N2-methylguanosine, cytidine and uridine. In certain embodiments, methods of measuring these biomarkers and kits for measuring these biomarkers are provided.
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- Reaction of arylnitrenium ions with guanine derivatives: N1-methylguanosine and N2,N2-dimethylguanosine
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A prior flash photolysis study of the direct reaction of arylnitrenium ions with 2′-deoxyguanosine identified a second intermediate that grew in as the transient nitrenium ion reacted with the nucleoside. This intermediate was identified as the the product of the addition of the nitrenium ion to the C-8 position of guanine prior to loss of the C-8 proton - the C-8 intermediate. A feature of the C-8 intermediate is that it exists in acid-base forms. This behavior was evident in both a spectroscopic analysis as well as in the rate-pH profile, which showed a break around pH 4 from a pH-independent reaction to a reaction that was first-order in H+. The present study was designed to identify the structure of the conjugate base form. This involved a kinetic study of the decay of the C-8 intermediate derived from the reaction of the 2-fluorenylnitrenium ion with N1-methylguanosine and N2,N2-dimethylguanosine. The rationale was that the former is unable to lose the N-1 proton, while the latter cannot deprotonate at the NH2 group. The rate-pH profiles clearly show that it is the N-1 proton that is acidic. The rate constants for the C-8 intermediate of N2,N2-dimethylguanosine show the same downward break observed with 2′-deoxyguanosine and guanosine associated with conversion to the conjugate base form. In contrast, the rate constants for the N1-methylguanosine intermediate are independent of pH. Rate constants for the reaction forming the C-8 intermediate are also reported. These show that the reaction of nitrenium ions with the N2,N2-dimethylguanine derivative is significantly faster (except where the reactions are diffusion controlled). This is consistent with the initial step of the reaction of an arylnitrenium ion and guanine occurring by direct addition at C-8. The developing positive charge in such a reaction can be delocalized to the C-2 position where π donors such as NH2 and NMe2 can exert a stabilizing effect.
- Cheng, Bernice,McClelland, Robert A.
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p. 1881 - 1886
(2007/10/03)
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- Chemical synthesis of a 5′-terminal TMG-capped triribonucleotide m32,2,7G5′ pppAmpUmpA of U1 RNA
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The 5′-terminal TMG-capped triribonucleotide, m32,2,7G5′pppAmpUmpA, has been synthesized by condensation of an appropriately protected triribonucleotide derivative of ppAmpUmpA with a new TMG-capping reagent. During this total synthesis, it was found that the regioselective 2′-O-methylation of 3′,5′-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-N-(4- monomethoxytrityl)adenosine was achieved by use of MeI/Ag2O without affecting the base moiety. A new route to 2-N,2-N-dimethylguanosine from guanosine via a three-step reaction has also been developed by reductive methylation using paraformaldehyde and sodium cyanoborohydride. These key intermediates were used as starting materials for the construction of a fully protected derivative of pAmpUmpA and a TMG-capping reagent of Im-pm32,2,7G. The target TMG-capped tetramer, m32,2,7G5′ pppAmpUmpA, was synthesized by condensation of a partially protected triribonucleotide 5′-terminal diphosphate species, ppAMMTrmpUmpA, with Im-pm32,2,7G followed by treatment with 80% acetic acid. The structure of m32,2,7G5′ pppAmpUmpA was characterized by 1H and 31P NMR spectroscopy as well as enzymatic assay using snake venom phosphodiesterase, calf intestinal phosphatase, and nuclease P1.
- Sekine, Mitsuo,Kadokura, Michinori,Satoh, Takahiko,Seio, Kohji,Wada, Takeshi,Fischer, Utz,Sumpter, Vicki,Lührmann, Reinhard
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p. 4412 - 4422
(2007/10/03)
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- A convenient method for the preparation of N2,N2-dimethylguanosine
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The preparation of N2,N2-dimethylguanosine is described. The use of the 2-(p-nitrophenyl)ethyl group instead of the benzyl protecting group for the O6 position of the guanine ring resulted in better yields and shorter protocols.
- Avino,Mayordomo,Espuny,Bach,Eritja
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p. 1613 - 1617
(2007/10/02)
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