1,721,044 research outputs found
Recent Progress in Chemically Modified siRNAs
No full textRNA interference technology has become a powerful laboratory tool to study gene function. Small interfering RNAs (siRNAs) have provided unprecedented opportunities for the development of new therapeutics in human diseases. Unfortunately, siRNA duplexes are not optimal drug-like molecules. The problems for their effective application are fundamentally delivery, stability and off-target effects. Chemical modification provides solutions to many of the challenges facing siRNA therapeutics. In this review, we recapitulate and discuss the development of the latest described chemical modifications of siRNAs, with a special focus on novel chemical modifications of siRNA structure, architecture and siRNA conjugates
SYNTHESIS OF 4-SUBSTITUTED PYRIMIDINE 2',3'-DIDEOXYNUCLEOSIDES
No full textReaction of 5'-O-(4,4'-dimethoxytriphenylmethyl)-3'-deoxythymidine with triphenylphosphine/carbon tetrachloride, followed by deprotection of the 5'-hydroxyl group, afforded the 4-chloro derivative 3 from which some 4-substituted pyrimidin-2(1H)one-2',3'-dideoxyribosides were obtained by nucleophilic substitution under very mild conditions. © 1991, Taylor & Francis Group, LLC. All rights reserved
SYNTHESIS OF CYCLIC BRANCHED OLIGODEOXYRIBONUCLEOTIDES
No full textThe cyclic branched oligodeoxyribonucleotides 7 and 8 have been prepared via the intermediate 4 synthesized using a phosphotriester approach
6-Chloroxanthosine, a useful intermediate for the efficient syntheses of [6-15N]-isoguanosine, isoinosine and other purine nucleoside analogues
No full text6-Chloroxanthosine 1, when activated towards nucleophilic displacement at the 6-C position by conversion into the corresponding 3-N-(2,4- dinitrophenyl) derivative 4, reacted with aq. 15NH3 to afford [6-15N]- isoguanosine 3b in 81% overall yield. Catalytic hydrogenation (Pd/C) of 1 led in 60 % yield to isoinosine 8; alternatively, this could be obtained in 88 % overall yield through alkaline hydrolysis of triphenylphosphonium salt 6, synthesized from 1 by reaction with PPh3. The reactivity of 1 was further explored by treating it with primary and secondary amines: the 6-N propylamino and the 6-N piperidinyl derivatives (5a and 5b, respectively) could thus both be prepared in more than 90 % yield
Improved synthesis of 2-, 3- -dideoxycytidine (d2c) and its correlated nucleoside analogues
No full text21, 31-dideoxy- and 2 13 ‘-dideoxy-21, 3 2-didehydrocy- tidine (d2C and d4C) have been synthesized in good yields from 21-deoxyuridine via dichlorinated derivatives 7ab. The same synthetic strategy was used in the synthesis of d2CMeand d4CMefrom thymidine. Following this method the evaluable 3*-chloro-21-deoxycytidine derivatives 9–12 can easily be obtained. © 1993, Taylor & Francis Group, LLC. All rights reserved
PNA-DNA chimeras forming quadruplex structures
No full textH-NMR, CD, and UV spectroscopy have been used to investigate the structure of PNA/DNA chimeras forming quadruplex structures. In particular, we synthesized 5′TGGG3′-t (1) and 5′TGG3′-gt (2), where lower and upper case letters indicate PNA and DNA residues, respectively. CD spectrum and all NMR data of (1) are typical of quadruplexes involving four parallel strands. UV melting profile of (1) indicates that its thermal stability is quite similar to that observed for the reference structure [d(TGGGT)]4. 1H-NMR spectrum for 5′TGG3′_gt (2) shows that this oligonucleotide is not able to fold into a single, well-defined species
Studies toward the synthesis of pinolidoxin, a phytotoxic nonenolide from the fungus Ascochyta pinodes. Determination of the configuration at the C-7, C-8, and C-9 chiral centers and stereoselective synthesis of the C-6-C-18 fragment
No full textThe absolute stereochemistry at the C-7, C-8, and C-9 chiral centers of pinolidoxin (1) has been determined by chemical and spectral methods. First, the synthesis of four stereoisomeric fully benzoylated 2,3-erythro-1,2,3,4- heptanetetrols, corresponding to the C6-C18 portion of the natural substance, has been accomplished starting from meso-tartaric acid. As next step, the selection of the synthetic tetrabenzoate possessing 'natural' stereochemistry (10a') suitable for absolute configuration determination, has been carried out by correlation with its 'natural' homologue derived from degradation of pinolidoxin. Determination of the stereochemistry at the title chiral centers has been carried out by application of the Mosher's method both to 7a', a compound stereochemically related to 10a', and to pinolidoxin itself. The stereoselective synthesis of a protected form of the C6-C18 portion of pinolidoxin, to be used in its total synthesis, has also been accomplished starting from commercially available D-erythronolactone
Nitration of cinnamic acids using cerium (IV) ammonium nitrate immobilized on silica
No full textTreatment of cinnamic acids with cerium (IV) ammonium nitrate supported on silica (CAN/SiO2) was used to synthesize nitro derivative and ipso substitution products. The position of the substituents defines the type and the yields of the products. This is the first example of an ipso substitution reaction by solid-phase approach
Inhibition of net nitrification activity in a Mediterranean woodland: Possible role of chemicals produced by Arbutus unedo
No full textNitrification is a key biological process for the control of soil NO 3- availability and N losses from terrestrial ecosystems. The study investigates the causes for the absence of net nitrification activity in the soil of a Mediterranean monospecific woodland of Arbutus unedo, focusing in particular on the possible role of chemicals produced by this plant. The mineral N pool, net rates of mineralization and nitrification were measured in the soil top 10 cm over 18 months. Raw extracts of leaves and roots of Arbutus unedo and soil underneath Arbutus plant canopy were purified using chromatographic techniques and the structure of chemicals was defined using spectroscopic and spectrometric methods. Leaf extracts (raw, aqueous and organic fractions) were tested for their toxicity on net nitrification, using a test soil. Field and laboratory incubations showed soil NO3- concentration below the detection limit over the whole study period, despite the significant NH4+ availability. Toxicity tests indicated that more than 400 μg of extract g-1 dry soil were needed to have more than 50% reduction of net NO3- production. Gallocatechin and catechin were among the most abundant chemicals in the extracts of leaves, roots and soil. Their soil concentration was significantly higher than the annual calculated input via leaf litter, and it was in the range of toxic concentrations, as deduced from the dose-response curve of the toxicity test. Data support the hypothesis that plant produced chemicals might be involved in the limited net nitrate production in this Mediterranean woodland. © 2008 Springer Science+Business Media B.V
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