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Modified Oligonucleotide (modified + oligonucleotide)

Distribution by Scientific Domains
Chemistry75%

Selected Abstracts

4-Thio-deoxyuridylate-modified thrombin aptamer and its inhibitory effect on fibrin clot formation, platelet aggregation and thrombus growth on subendothelial matrix

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 10 2008
S. MENDELBOUM RAVIV
Summary.,Background:,The consensus thrombin aptamer C15-mer is a single-stranded DNA of 15 nucleotides [d(GGTTGGTGTGGTTGG)] that was identified by the selection of thrombin-binding molecules from a large combinatorial library of oligonucleotides. It is capable of inhibiting thrombin at nanomolar concentrations through binding to a specific region within thrombin exosite 1. As has been shown in our earlier studies, the 4-thio-deoxyuridylate (s4dU)-containing oligonucleotides have high affinity for a number of proteins, due to the reduced hydrophilic character of the modified oligonucleotide. Methods:,Three different analogs of the original thrombin-inhibiting sequence, in which some of the thymidylate residues were replaced by 4-thio-deoxyuridylates, were synthesized. The inhibitory effect of modified aptamers was tested on thrombin-catalyzed fibrin clot formation and fibrinopeptide A release from fibrinogen, thrombin-induced platelet aggregation/secretion, and the formation of thrombus on coverslips coated with human collagen type III, thrombin-treated fibrinogen or subendothelial matrix of human microvascular endothelial cells. Results:,As compared with the C15-mer, the analog with the sequence GG(s4dU)TGG(s4dU)G(s4dU)GGT(s4dU)GG (UC15-mer) showed a 2-fold increased inhibition of thrombin-catalyzed fibrin clot formation, fibrinopeptide A release, platelet aggregation and secretion in human plasma and thrombus formation on thrombin-treated fibrinogen surfaces under flow conditions. Concerning the inhibition of thrombin-induced fibrin formation from purified fibrinogen and activation of washed platelets, UC15-mer was 3-fold and twelve-fold more effective than C15-mer, respectively. Conclusion:,The replacement of four thymidylate residues in C15-mer by 4-thio-deoxyuridylate resulted in a new thrombin aptamer with increased anticoagulant and antithrombotic properties. [source]

Intra- and Intermolecular Interactions Influence the Reactivity of RNA Oligonucleotides

CHEMISTRY & BIODIVERSITY, Issue 12 2007
Heidi Linjalahti
Abstract The transesterification of RNA oligonucleotides was studied over a wide pH range. The rate constants obtained indicate that, under neutral conditions, oligonucleotides with an adenosine moiety as the 5,-linked nucleoside can be up to 1000-fold more reactive than the reference oligonucleotide, a 13-mer oligo-U (1). Experiments with the modified oligonucleotide with N6,N6 -dimethyladenosine (9) as the 5,-linked nucleoside moiety suggest that the exocyclic amino group is involved in the reaction, influencing the reactivity of the neighboring phosphodiester bond. In addition to such intramolecular interactions, weak intermolecular interactions most probably contribute to the reactivity. [source]

Oligonucleotides Containing 7-Deaza-2,-deoxyinosine as Universal Nucleoside: Synthesis of 7-Halogenated and 7-Alkynylated Derivatives, Ambiguous Base Pairing, and Dye Functionalization by the Alkyne,Azide ,Click' Reaction

HELVETICA CHIMICA ACTA, Issue 7 2008
Frank Seela
Abstract Oligonucleotides containing 7-deaza-2,-deoxyinosine derivatives bearing 7-halogen substituents or 7-alkynyl groups were prepared. For this, the phosphoramidites 2b,2g containing 7-substituted 7-deaza-2,-deoxyinosine analogues 1b,1g were synthesized (Scheme,2). Hybridization experiments with modified oligonucleotides demonstrate that all 2,-deoxyinosine derivatives show ambiguous base pairing, as 2,-deoxyinosine does. The duplex stability decreases in the order Cd>Ad>Td>Gd when 2b,2g pair with these canonical nucleosides (Table,6). The self-complementary duplexes 5,-d(F7c7I-C)6, d(Br7c7I-C)6, and d(I7c7I-C)6 are more stable than the parent duplex d(c7I-C)6 (Table,7). An oligonucleotide containing the octa-1,7-diyn-1-yl derivative 1g, i.e., 27, was functionalized with the nonfluorescent 3-azido-7-hydroxycoumarin (28) by the Huisgen,Sharpless,Meldal cycloaddition ,click' reaction to afford the highly fluorescent oligonucleotide conjugate 29 (Scheme,3). Consequently, oligonucleotides incorporating the derivative 1g bearing a terminal CC bond show a number of favorable properties: i) it is possible to activate them by labeling with reporter molecules employing the ,click' chemistry. ii) Space demanding residues introduced in the 7-position of the 7-deazapurine base does not interfere with duplex structure and stability (Table,8). iii) The ambiguous pairing character of the nucleobase makes them universal probes for numerous applications in oligonucleotide chemistry, molecular biology, and nanobiotechnology. [source]

Synthesis of Encoded Modified Oligonucleotide Libraries.

CHEMISTRY & BIODIVERSITY, Issue 4 2004

The basis for further development of combinatorial libraries of modified oligonucleotides tagged by a codifying sequence is discussed. The chemistry involved in the orthogonal synthesis of both strands and some representative examples of building blocks are presented. [source]