1,721,079 research outputs found
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
G-quadruplex-based aptamers targeting human thrombin: Discovery, chemical modifications and antithrombotic effects
No full textFirst studies on thrombin-inhibiting DNA aptamers were reported in 1992, and since then a large number of anticoagulant aptamers has been discovered. TBA – also named HD1, a 15-mer G-quadruplex (G4)-forming oligonucleotide – is the best characterized thrombin binding aptamer, able to specifically recognize the protein exosite I, thus inhibiting the conversion of soluble fibrinogen into insoluble fibrin strands. Unmodified nucleic acid-based aptamers, in general, and TBA in particular, exhibit limited pharmacokinetic properties and are rapidly degraded in vivo by nucleases. In order to improve the biological performance of aptamers, a widely investigated strategy is the introduction of chemical modifications in their backbone at the level of the nucleobases, sugar moieties or phosphodiester linkages. Besides TBA, also other thrombin binding aptamers, able to adopt a well-defined G4 structure, e.g. mixed duplex/quadruplex sequences, as well as homo- and hetero-bivalent constructs, have been identified and optimized. Considering the growing need of new efficient anticoagulant agents associated with the strong therapeutic potential of these thrombin inhibitors, the research on thrombin binding aptamers is still a very hot and intriguing field. Herein, we comprehensively described the state-of-the-art knowledge on the DNA-based aptamers targeting thrombin, especially focusing on the optimized analogues obtained by chemically modifying the oligonucleotide backbone, and their biological performances in therapeutic applications
Disentangling the Structure-Activity Relationships of Naphthalene Diimides as Anticancer G-Quadruplex-Targeting Drugs
Full text linkIn the context of developing efficient anticancer therapies aimed at eradicating any sort of tumors, G-quadruplexes
represent excellent targets. Small molecules able to interact with G-quadruplexes can interfere with cell pathways specific of tumors and common to all cancers. Naphthalene diimides (NDIs) are among the most promising, putative anticancer G-quadruplextargeting drugs, due to their ability to simultaneously target multiple G-quadruplexes and their strong, selective in vitro and in vivo anticancer activity. Here, all the available biophysical, biological, and structural data concerning NDIs targeting Gquadruplexes were systematically analyzed. Structure−activity correlations were obtained by analyzing biophysical data of their interactions with G-quadruplex targets and control duplex structures, in parallel to biological data concerning the antiproliferative activity of NDIs on cancer and normal cells. In addition, NDI binding modes to G-quadruplexes were discussed in consideration of the structures and properties of NDIs by in-depth analysis of the available structural models of G-quadruplex/NDI complexes
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
CALORIMETRIC, SPECTROSCOPIC AND COMPUTATIONAL INVESTIGATION ON DNA TRIPLEXES CONTAINING 3',3'INTERNUCLEOSIDE JUNCTION
No full textDesign, Synthesis, and Characterization of an Amphiphilic Lipoic Acid-Based Ru(III) Complex as a Versatile Tool for the Functionalization of Different Nanosystems
Full text linkRu-based chemotherapy is emerging as an effective alternative to the well-established Pt-based one, typically associated with high toxicity. In this context, our recent efforts were devoted to the preparation of nucleolipid-based Ru(III) complexes able to form, under physiological conditions, supramolecular aggregates which can efficiently prevent metal deactivation and convey Ru(III) inside the cells where it exerts its activity. Within an interdisciplinary program for the development of multifunctional nanoparticles for theranostic applications, we here report the design, synthesis, and characterization of a novel functionalized Ru(III) salt, carrying a lipoic acid moiety in the nucleolipid-based scaffold to allow its incorporation onto metal-based nanoparticles
CALORIMETRIC, SPECTROSCOPIC AND COMPUTATIONAL INVESTIGATION ON DNA TRIPLEXES CONTAINING 3',3'INTERNUCLEOSIDE JUNCTION
No full text6-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
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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