16,871 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
An alternative strategy to synthesize PNA and DNA magnetic conjugates forming nanoparticle assembly based on PNA/DNA duplexes
No full textIn this paper we report an alternative approach to synthesize PNA and DNA magnetic nanoconjugates. Chemical modifications were introduced on the 130 nm dextran-magnetite particles to obtain poly-functionalized particles containing reversible bonds sensitive to the cellular environment and suitable for the direct introduction of unmodified oligomers. Due to the polyvalent nature of the nanoparticles, when the complementary PNA and DNA nanoconjugates were mixed together, the resulting duplex structures bring to a nanoparticle assembly driven by W-C base pairs. The formation of the nanoparticle assembly was investigated by optical spectroscopy (UV, FTIR), scanning and transmission electron microscopies and by the analysis of the macroscopic behaviour of the nanoparticle-conjugates in aqueous solution with and without magnetic field application. Furthermore, serum stability assays revealed an increased enzymatic resistance in FCS of the PNA/DNA nanoconjugate duplex with respect to the unconjugated duplex. The described nanosystem could be extended to other duplex structures, possibly involving aptameric sequences of biomedical relevance, and could be very useful in order to obtain high local concentration at the target site of both the duplex and the magnetic nanoparticles in biotechnological applications
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
Current Methods in Synthesis of Cyclic Oligonucleotides and Analogues
No full textCyclic oligonucleotides and analogues (cONs) are highly specific ligands for DNA, RNA and proteins. cONs are described in several diagnostic and therapeutic applications, as well as in elucidating enzyme mechanisms and as lead structures for development of new drugs because of their unusual chemical and biological properties in comparison with linear counterparts. In numerous structural studies it has been shown that conformational constraints imposed by circularity cause unique topologies, which in some cases can result into peculiar ON nanostructures. The wide field of applications of cONs has called for the definition of easy and efficient strategies to produce such compounds.
In this review, we will describe the enzymatic and chemical approaches reported for the synthesis of cONs with a particular focus on the chemical ones. We proceed following a chronological order from the earliest to the latest methods and improvements, describing at first the natural cyclic ONs and then modified linkages and cyclic analogues
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
Synthesis of 2',3'-dideoxy-2',3'-didehydronucleosides analogues as potential anti HIV agents
No full textThe 4-substituted pyrimidine 2′,3′-dideoxy-2′,3′-didehydronucleosides (4–10) have been synthesized via intermediate 3
Synthetic studies on the glycosylation of the base residues of inosine and uridine
No full textRibosylation and glucosylation of the base residues of inosine and uridine have been efficiently achieved using Mitsunobu reaction, leading to the N-1 and 6-O-glycosylinosine and N-3-glycosyluridine derivatives, all with β configuration at the glycosidic carbon. The unprecedented 5-amino-1-(β-D-ribofuranosyl)imidazole-4-[N-(β-D-glucopyranosyl) carboxamide] has also been synthesised. © The Royal Society of Chemistry 1999
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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