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Search for "oligonucleotides" in Full Text gives 96 result(s) in Beilstein Journal of Organic Chemistry.
Nucleoside macrocycles formed by intramolecular click reaction: efficient cyclization of pyrimidine nucleosides decorated with 5'-azido residues and 5-octadiynyl side chains
Beilstein J. Org. Chem. 2018, 14, 2404–2410, doi:10.3762/bjoc.14.217
- analysis of the cyclic ketones muscone and civetone [1]. Other classical examples are cyclic peptides such as valinomycin and cyclic oligosaccharides like cyclodextrins [2][3][4]. The literature has been recently reviewed [5]. Also, oligonucleotides form cyclic structures commonly existing in plasmid DNA
- and deprotection steps are necessary to control the cyclization process. Preorganization of the molecules can help to make cyclization more efficient. Azide–alkyne "click" chemistry has been executed to generate cyclic peptides [11][12][13], cyclic oligonucleotides [14][15][16][17] and other
- display increased lipophilicity they have the potential to be utilized for the transmembrane delivery of nucleotides and oligonucleotides. More important, all of the macrocyle moieties and the size of the macrocycle can be altered. The system can be regarded as a new lead for further structural and
Artificial bioconjugates with naturally occurring linkages: the use of phosphodiester
Beilstein J. Org. Chem. 2018, 14, 1946–1955, doi:10.3762/bjoc.14.169
- elaborate bioconjugates. Herein, we describe the use of a phosphodiester bond as a versatile option to access various bioconjugates. An opposite activation strategy, involving 5’-phosphitylation of the supported oligonucleotides, has allowed several biomolecules that possess an unactivated alcohol to be
- ’-phosphitylation; phosphodiester bonds; Introduction Peptides and oligonucleotides are of exceptional importance since they are promising pharmaceutical candidates for the treatment of a range of diseases that are beyond traditional small molecule drugs [1][2][3][4][5][6][7]. Due to their iterative structures
- artificial building blocks with various functions are available, expanding chemical libraries of peptides and oligonucleotides significantly [8][9][10][11][12][13][14][15]. Furthermore, thus designed and synthesized peptides and oligonucleotides can be conjugated with each other to integrate their
Synthesis and photophysical studies of a multivalent photoreactive RuII-calix[4]arene complex bearing RGD-containing cyclopentapeptides
Beilstein J. Org. Chem. 2018, 14, 1758–1768, doi:10.3762/bjoc.14.150
- activity of enzymes such as RNA polymerase or endonuclease is inhibited in vitro at the level of the photoadduct [23][24]. In order to target a specific DNA sequence, photoreactive RuII complexes have been anchored to specific antisense oligonucleotides to inhibit the expression of the complementary
Phosphoramidite building blocks with protected nitroxides for the synthesis of spin-labeled DNA and RNA
Beilstein J. Org. Chem. 2018, 14, 1563–1569, doi:10.3762/bjoc.14.133
- could be incorporated by unmodified standard procedures into four different self-complementary DNA and two RNA oligonucleotides. After photochemical removal of the protective group, elimination of formic aldehyde and spontaneous air oxidation, the nitroxide radicals were regenerated in high yield. The
- required to assemble oligonucleotides by phosphoramidite chemistry and to ligate them enzymatically, are known to partially degrade nitroxides. This problem can be reduced by postsynthetic introduction of the spin label [13][14][15][16][17][18][19][20][21][22][23][24]. Starting from convertible nucleotides
- oligonucleotides by phosphoramidite building blocks [27][28][29][30][31][32][33][34][35][36][37][38][39][40]. However, some degradation of the spin labels inevitably will occur. Nitroxide labeled DNA strands of the general structures 2 and 4 have been prepared by this way [30][34][37]. In recent years, we have
Oligonucleotide analogues with cationic backbone linkages
Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111
- Melissa Meng Christian Ducho Department of Pharmacy, Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C2 3, 66123 Saarbrücken, Germany 10.3762/bjoc.14.111 Abstract Their unique ability to selectively bind specific nucleic acid sequences makes oligonucleotides promising
- bioactive agents. However, modifications of the nucleic acid structure are an essential prerequisite for their application in vivo or even in cellulo. The oligoanionic backbone structure of oligonucleotides mainly hampers their ability to penetrate biological barriers such as cellular membranes. Hence
- , particular attention has been given to structural modifications of oligonucleotides which reduce their overall number of negative charges. One such approach is the site-specific replacement of the negatively charged phosphate diester linkage with alternative structural motifs which are positively charged at
An overview of recent advances in duplex DNA recognition by small molecules
Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93
Phosphodiester models for cleavage of nucleic acids
Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68
- , whereas with ribonucleoside 3´-phosphodiesters both hydroxy functions are secondary. Accordingly, extrapolation of the results obtained with 1 to the cleavage of nucleic acids is not straightforward. Care should be exercised to avoid misinterpretations. Oligonucleotides containing a thiosubstituted
- necessary background information for the studies with thiosubstituted oligonucleotides has been obtained by comparative studies with similar analogs of dinucleoside-3´,5´-monophosphates [43]. Cleavage of RNA by Brönsted acids and bases Buffer-independent reactions The predominant buffer-independent
- introductory part, phosphorothiolate oligonucleotides containing a bridging 3´- or 5´-thiosubstitution, are used as mechanistic probes of enzyme catalysis. Non-bridging thiosubstitution, in turn, creates RP and SP diastereomeric phosphorothioate linkages which have extensively been used for elucidation of the
Enzyme-free genetic copying of DNA and RNA sequences
Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47
- suggest that enzyme-free primer extension is a more powerful reaction than previously thought. Keywords: base pairing; DNA; enzyme-free primer extension; nucleotides; oligonucleotides; replication; RNA; Introduction Replication of genetic information is critical for all living systems. In the cell, this
- strands catalyze splicing or ligation of longer oligonucleotides [3][4]. Ancient ribozymes might have acted as polymerases [5], inducing either the oligomerization of activated ribonucleotides or the replication of the first RNA genomes. But ribozymes are usually too long to be likely to emerge from
- (Figure 2), and assay buffers containing high concentrations of Mg2+ ions [15]. When advances in automated solid-phase synthesis made oligonucleotides of any given sequence readily available [16], copying reactions involving the extension of a primer bound to a specific sequence of hairpins mimicking this
Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing
Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32
- Francoise Debart Christelle Dupouy Jean-Jacques Vasseur IBMM, Université de Montpellier, CNRS, ENSCM, Montpellier, France 10.3762/bjoc.14.32 Abstract Oligonucleotides (ONs) have been envisaged for therapeutic applications for more than thirty years. However, their broad use requires overcoming
- group; oligonucleotide prodrugs; reduction-responsive; stimuli-responsive nucleic acids; thermolytic prodrugs; Introduction For past decades, oligonucleotide-based therapies have been widely developed using short synthetic oligonucleotides (ONs) and their chemically modified mimics as powerful tools to
- strategies include antisense oligonucleotides (AONs), ribozymes, DNAzymes, small interfering RNAs (siRNAs) and micro RNAs (miRNAs) that specifically target the complementary mRNA sequence of the relevant undesired gene before translation. AONs are single-stranded DNA of 15 to 25 nucleotides in length that
Preparation of trinucleotide phosphoramidites as synthons for the synthesis of gene libraries
Beilstein J. Org. Chem. 2018, 14, 397–406, doi:10.3762/bjoc.14.28
- partially circumvent this problem, like using NNS instead of NNN codons (with N = A, C, G, T; S = C, G) taking advantage of redundancy of the third nucleotide positions in the majority of codons [10], or using spiked oligonucleotides [11], which are synthesized from solutions of the four nucleotide building
- phosphitylation to be used in standard DNA synthesis. The preparation of mixed oligonucleotides for random mutagenesis including the strategy of using trinucleotide synthons has been reviewed recently [19][24]. Therefore, herein we will concentrate on more recent developments in trinucleotide synthesis. Review 1
- polystyrene support decorated with a photolabile linker and its potential use for the synthesis of siRNA duplexes under mild and neutral conditions [36]. A similar strategy was used for the synthesis of partially 2'/3'-O-acetylated RNA oligonucleotides [37]. A photo-cleavable linker would also have potential
Fluorogenic PNA probes
Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17
- and biological stabilities in addition to their ability to bind to structured nucleic acid targets. In addition, the uncharged backbone of PNA allows for other unique designs that cannot be performed with oligonucleotides or analogues with negatively-charged backbones. This review aims to introduce
- transduction and readout strategies have been developed, even for fluorescence-based detection alone, the recognition element of the probe is almost always an oligodeoxynucleotide. During the past few decades, there have been continuous developments of unnatural oligonucleotides with superior properties that
- (aeg) backbone that can recognize its target DNA and RNA was reported [21]. Considering the enormous difference between the two backbones, it is quite surprising that PNA can still retain the ability to recognize natural oligonucleotides having a complementary sequence with high affinity and
Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications
Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7
- functionalized with a phosphoramidite and incorporated into oligonucleotides [30]. However, the fully detailed synthesis with complete characterization was published in 2007 as a Nature Protocol paper [37]. The aromatic core of tC was prepared according to the procedure of Roth et al. (Scheme 1), followed by a
- % yield of 37 after TFA deprotection of the Boc group compared to the previously reported 96% [51]. The base-pairing properties of qA with T and selectivity were found to be excellent. Moreover, the melting temperature of the oligonucleotides remained close to those of unmodified sequences indicating that
- ., pointing towards the nitro group) [14]. As was mentioned in the synthesis part above, recently we also have developed tCO as an internal fluorophore for RNA systems [50]. The incorporation into RNA oligonucleotides and hybridization with a complementary strand results in normal A-form RNA duplexes
Polarization spectroscopy methods in the determination of interactions of small molecules with nucleic acids – tutorial
Beilstein J. Org. Chem. 2018, 14, 84–105, doi:10.3762/bjoc.14.5
- guanine quadruplexes is discussed in chapter 3. 2.2. DNA or RNA stock solution preparation Here we discuss in detail only polynucleotides with lengths of more than 100 base pairs because oligonucleotides with known composition are much easier to dissolve, to check their structural properties and to
- determine exact concentrations. Also, short oligonucleotides can fail in representing a biologically significant structural model, because of heterogeneous binding sites due to the “capping” effect, whereby a ligand can bind similarly to the end base pairs and to a binding site along the helix [19
Synthetic mRNA capping
Beilstein J. Org. Chem. 2017, 13, 2819–2832, doi:10.3762/bjoc.13.274
- and limitations of the different strategies and – if available – will show ways to circumvent them. This review focuses strictly on mRNA cap analogues (and some non-natural modifications); for preparation of other capped biomolecules such as capped siRNAs [21], peptidyl capped oligonucleotides [22
Metal-mediated base pairs in parallel-stranded DNA
Beilstein J. Org. Chem. 2017, 13, 2671–2681, doi:10.3762/bjoc.13.265
- direction of the oligonucleotide chains are also known as Westhof’s rule [52]. Chimeric base pairs of α- and β-deoxyribonucleosides Another possibility to create parallel-stranded duplexes is the use of α-anomeric nucleic acids. These oligonucleotides are formally derived via an inversion of the
- Hoogsteen (rather than reversed Hoogsteen) base pairing could not be ruled out completely for this parallel-stranded duplex, so that in principle a cisoid εA–Ag(I)2–εA base pair may also form when the complementary oligonucleotides are aligned in a parallel fashion. However, considering the intrinsic
- stabilizing in an antiparallel-stranded duplex for 12-mer oligonucleotides, whereas longer 25-mers showed a larger stabilization in a parallel-stranded orientation. Nonetheless, the use of parallel-stranded duplexes significantly extents the scope of metal-mediated base pairing, because it has been shown that
Pyrene–nucleobase conjugates: synthesis, oligonucleotide binding and confocal bioimaging studies
Beilstein J. Org. Chem. 2017, 13, 2521–2534, doi:10.3762/bjoc.13.249
- compounds. The conjugates bearing a carbonyl function represent weak emitters as compared to compounds with a hydroxy function in the linker. The self-assembly properties of pyrene nucleobases were investigated in respect to their binding to single and double strand oligonucleotides in water and in buffer
- pyrene 1ππ* state). Thus, intersystem crossing between these two states can be efficient giving rise to also efficient radiationless depopulation of the emissive singlet state relative to aliphatic analogues, in that quenching 3nπ* states are not present. Interactions with oligonucleotides Compounds 2–5
- investigate the interactions between the compounds 2–5 when they bind specifically to a given DNA template. The titration experiments were performed with single and double-stranded oligonucleotides. The interactions between the chromophores and a 10-mer of the single-stranded oligo-2’-deoxyadenosine, (dA)10
Framing major prebiotic transitions as stages of protocell development: three challenges for origins-of-life research
Beilstein J. Org. Chem. 2017, 13, 1388–1395, doi:10.3762/bjoc.13.135
- membrane components. These protocells, hypothetically making use of the first ‘energy transduction mechanisms’ (leading to precursor ‘energy currencies’ – based on thioesters [62] and/or pH gradients [53], for instance) and a metabolism that incorporated oligonucleotides and oligopeptides (to become RNA
Synthesis of oligonucleotides on a soluble support
Beilstein J. Org. Chem. 2017, 13, 1368–1387, doi:10.3762/bjoc.13.134
- Harri Lonnberg Department of Chemistry, University of Turku, FIN-20014 Turku, Finland 10.3762/bjoc.13.134 Abstract Oligonucleotides are usually prepared in lab scale on a solid support with the aid of a fully automated synthesizer. Scaling up of the equipment has allowed industrial synthesis up
- . Several of protocols developed for the soluble-supported synthesis allow the preparation of both DNA and RNA oligomers of limited length in gram scale without any special equipment, being evidently of interest for research groups that need oligonucleotides in large amounts for research purposes. However
- , none of them has really tested at such a scale that the feasibility of their industrial use could be critically judged. Keywords: DNA; oligonucleotides; RNA; soluble support; synthesis; Introduction The synthesis of oligonucleotides (ONs) consists of linking nucleosides to each other in a specified
Biomimetic molecular design tools that learn, evolve, and adapt
Beilstein J. Org. Chem. 2017, 13, 1288–1302, doi:10.3762/bjoc.13.125
- , and peptides and oligonucleotides can also be synthesized efficiently using automated methods, it is not yet possible to carry out chemical syntheses in a general sense using these technologies. However, several groups are making significant breakthroughs in generalizing and expanding the automated
Towards open-ended evolution in self-replicating molecular systems
Beilstein J. Org. Chem. 2017, 13, 1189–1203, doi:10.3762/bjoc.13.118
- catalyzing the formation of biopolymers [31][32]. Von Kiedrowski et al. were able to demonstrate exponential growth of oligonucleotides using a method that they gave the eloquent anagram; SPREAD (Surface-Promoted Replication and Exponential Amplification of DNA analogues) [33]. In the SPREAD technique
- . 3.3 RNA self-replication Owing to the importance of RNA in viral species and in the origin of life, evolution experiments are most often performed using RNA molecules or closely related derivatives. In fact, it has become possible to perform natural selection on oligonucleotides by iterative
- ribozymes. The observed cooperative behavior relies on recognition strands and tags, so that it will only play a role for the assembly of intermediate-sized oligonucleotides. Small oligonucleotides would likely still replicate more efficiently via auto or cross catalytic cycles. At a certain length scale
DMAP-assisted sulfonylation as an efficient step for the methylation of primary amine motifs on solid support
Beilstein J. Org. Chem. 2017, 13, 806–816, doi:10.3762/bjoc.13.81
- Methylated amines and amides are common motifs found in natural and synthetic compounds, e.g., small molecules, peptides, and oligonucleotides [1][2][3][4][5][6][7][8]. Methylation of amines and amides has found many applications in the fields of pharmacological research, materials science, and in synthetic
A postsynthetically 2’-“clickable” uridine with arabino configuration and its application for fluorescent labeling and imaging of DNA
Beilstein J. Org. Chem. 2017, 13, 127–137, doi:10.3762/bjoc.13.16
- by blue and green emitting cyanine-styryl dyes were improved due to the arabino-configured anchor. These oligonucleotides were used as energy transfer donors in hybrids with oligonucleotides modified with acceptor dyes that emit in the yellow-red range. These combinations give energy transfer pairs
- DNA polymerases in primer extension experiments and PCR [4][16]. To develop fluorescently labelled oligonucleotides that undergo energy transfer reactions [17] we recently applied 2’-propargyl-modified uridine 1 as DNA building block (Scheme 1) [15][18][19]. A simple look on the three-dimensional
- structure of double-helical DNA elucidates that the positioning of the fluorophores in the major groove may be improved by inversion of the configuration at the 2’-position of the anchor nucleoside sugar. In fact, arabino nucleic acids are an important class of antisense oligonucleotides [20] since their
Enzymatic synthesis and phosphorolysis of 4(2)-thioxo- and 6(5)-azapyrimidine nucleosides by E. coli nucleoside phosphorylases
Beilstein J. Org. Chem. 2016, 12, 2588–2601, doi:10.3762/bjoc.12.254
- comparison with the natural pyrimidine nucleosides in order to understand the impact of such modifications as monomers or constituents of oligonucleotides [8][9][10][11][12][13][14]. Thioxopyrimidine nucleosides as such, as well as building blocks of artificial oligonucleotides demonstrate promising
DNA functionalization by dynamic chemistry
Beilstein J. Org. Chem. 2016, 12, 2136–2144, doi:10.3762/bjoc.12.203
- generate libraries of molecules from simpler building blocks by reversible reactions under thermodynamic control. Here we focus on the chemical modification of DNA oligonucleotides with acyclic diol linkers and demonstrate their potential for the deoxyribonucleic acid functionalization and generation of
- oligonucleotides. The amino group containing phosphoramidite was used together with complementary single-strand DNA templates that influenced the Watson–Crick base-pairing equilibrium in the mixture with a set of aldehyde modified nucleobases. A significant fraction of all possible base-pair mismatches was
- oligonucleotides an ideal supramolecular scaffold in a wide field of applications [1][2]. In recent years oligonucleotides especially were applied to self-assembly into artificial nanostructures [3][4][5][6][7][8][9]. Preparation of oligonucleotides for new applications requires the introduction of additional
Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA
Beilstein J. Org. Chem. 2016, 12, 1348–1360, doi:10.3762/bjoc.12.128
- synthesis of conjugates of pyrrole–imidazole polyamide minor groove binders (MGB) with fluorophores and with triplex-forming oligonucleotides (TFOs). Diverse bifunctional linkers were synthesized and used for the insertion of terminal azides or alkynes into TFOs and MGBs. The formation of stable triple
- –imidazole polyamides; sequence specificity: DNA; triplex-forming oligonucleotides; Introduction The recognition and detection of specific sequences in native genomic double-stranded DNA (dsDNA) is of significant importance for the development of efficient gene therapies and in vivo gene labeling [1][2][3
- ]. Besides natural and engineered peptides or proteins, two synthetic substances are known to recognize and bind dsDNA in a sequence-specific manner: triplex-forming oligonucleotides (TFOs) [4][5] and pyrrole–imidazole polyamide minor groove binders (MGBs) [6][7]. TFOs recognize polypurine stretches in
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