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Special Issue "Nucleic Acid Analogs"

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A special issue of Molecules (ISSN 1420-3049).

Deadline for manuscript submissions: closed (31 October 2012)

Special Issue Editor

Guest Editor
Prof. Dr. Lajos Kovacs

Nucleic Acids Laboratory, Department of Medicinal Chemistry, Universtiy of Szeged, Dóm tér 8, H-6720 Szeged, Hungary
Website | E-Mail
Fax: +36 62 42 59 71
Interests: G quadruplexes; supramolecular chemistry; synthetic organic chemistry of carbohydrates; nucleobases; nucleosides; C-nucleosides; peptide nucleic acids; heterocycles; protecting groups

Special Issue Information

Dear Colleagues,

The naissance and development of molecular biology has greatly benefited from the support of the chemistry of  important biomolecules (amino acids, peptides, proteins, carbohydrates, nucleic acids). This fact may sound trivial for chemists but it has not been widely acknowledged by the practitioners of modern biology. Consequently, chemistry has long been considered as an auxiliary science of biology. Indeed, the methods routinely used in contemporary biological research largely rely on developments from fields outside the scope of biology itself, mainly from chemical, physical and IT sciences. This is a fortunate synergy among fields seemingly far from each other.

Chemistry, however, is a science in its own right, with aims and scopes originating not only from other disciplines but from the curiosity of its pursuers. The role of nucleic acids has been firmly established since the deciphering of double helix structure of DNA and the above outlined tremendous development of molecular biology methods with huge impact on other fields as well. The contribution of nucleic acid chemistry to this success is not ceasing, just remember the everyday use of DNA sequencing methods. Along with this development, nucleic acid research is taking new directions as well: synthesis of even more complex molecules like RNA, synthetic analogues (peptide nucleic acids, locked nucleic acids, morpholino oligos, conjugates etc.), superior analytical methods (e.g. those based on mass spectrometry), study of higher-order structures (triple and quadruple helices), investigation of molecular electronic devices based on nucleic acid analogues, to name just a few. I would like to cordially invite everyone involved it his exciting field and to contribute to the success of our Special Issue "Nucleic Acid Analogs" by presenting her/his results.

Prof. Dr. Lajos Kovacs
Guest Editor

Keywords

adenine; adenosine; ADP; AMP; antigene; antisense; antiviral activity; aptamer; asthma; ATP; avidin; beacons; bioconjugation; biosensor; biotin; branched oligonucleotides; cAMP; capillary gel-electrophoresis; carbon-paste electrodes; cationic liposomes; CDP; cellular uptake; cleaving DNAzyme; click chemistry; CMP; colloidal gold nanoparticles; colorimetric detection; combinatorial chemistry; copper(i)-catalyzed azide-alkyne reaction; crossover molecules; CTP; cycloadditions; cytosine; cytidine; density oligonucleotide arrays; Diels-Alder bioconjugation; directed synthesis; disposable DNA; DNA microarrays; DNA synthesis; DNA triple-helix; DNA-directed immobilization; double-stranded DNA; double-stranded RNA; drug-delivery; electrochemical detection; electrochemical stripping detection; fluorescent oligonucleotides; GDP; gene delivery; GMP; gold electrode; gold surfaces; GTP; guanine; guanosine; HCMV; HIV; HSV; human telomerase; human-immunodeficiency-virus; hybridization; immo bilization; intracellular delivery ; in-vitro selection; light-up probes; LNA; locked nucleic-acids; magnet assisted transfection; magnetic gene transfection; magnetic nanoparticles ; mass-spectrometry; microarray; molecular recognition; morpholino analogues; nanoparticles; NF-kappa-b; nucleic-acid based technology; nucleobases; nucleosides; nucleotides; oligonucleotide dendrimers; oligonucleotide synthesis; on-column conjugation; peptide nucleic acid; phosphorothioate oligodeoxynucleotides; pH-sensitive liposomes; plasmid-DNA; PNA; PNA molecular beacons; quadruplex nucleic acids reversible polymers; RNA interference; RNA liposomes; RNA synthesis; self-assembled monolayers (SAM); self-assembly; sensor; short interfering RNA; shRNA; single-nucleotide polymorphisms; siRNA; site-specific modification; small interfering RNA; SNP; streptavidin; surface-plasmon resonance; switching signaling aptamers; synthesis; TDP; templated organic synthesis; thymine; thymidine; TMP; transcript ion factor; TTP; UDP; UMP; uracil; uridine; UTP; viral vectors; voltammetry; walled carbon nanotubes

Related Special Issue

Published Papers (20 papers)

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Research

Jump to: Review

Open AccessArticle Synthesis and Biological Evaluation of Triazolyl 13α-Estrone–Nucleoside Bioconjugates
Molecules 2016, 21(9), 1212; doi:10.3390/molecules21091212
Received: 28 July 2016 / Revised: 2 September 2016 / Accepted: 6 September 2016 / Published: 10 September 2016
PDF Full-text (2934 KB) | HTML Full-text | XML Full-text
Abstract
2′-Deoxynucleoside conjugates of 13α-estrone were synthesized by applying the copper-catalyzed alkyne–azide click reaction (CuAAC). For the introduction of the azido group the 5′-position of the nucleosides and a propargyl ether functional group on the 3-hydroxy group of 13α-estrone were chosen. The best yields
[...] Read more.
2′-Deoxynucleoside conjugates of 13α-estrone were synthesized by applying the copper-catalyzed alkyne–azide click reaction (CuAAC). For the introduction of the azido group the 5′-position of the nucleosides and a propargyl ether functional group on the 3-hydroxy group of 13α-estrone were chosen. The best yields were realized in our hands when the 3′-hydroxy groups of the nucleosides were protected by acetyl groups and the 5′-hydroxy groups were modified by the tosyl–azide exchange method. The commonly used conditions for click reaction between the protected-5′-azidonucleosides and the steroid alkyne was slightly modified by using 1.5 equivalent of Cu(I) catalyst. All the prepared conjugates were evaluated in vitro by means of MTT assays for antiproliferative activity against a panel of human adherent cell lines (HeLa, MCF-7 and A2780) and the potential inhibitory activity of the new conjugates on human 17β-hydroxysteroid dehydrogenase 1 (17β-HSD1) was investigated via in vitro radiosubstrate incubation. Some protected conjugates displayed moderate antiproliferative properties against a panel of human adherent cancer cell lines (the protected cytidine conjugate proved to be the most potent with IC50 value of 9 μM). The thymidine conjugate displayed considerable 17β-HSD1 inhibitory activity (IC50 = 19 μM). Full article
(This article belongs to the collection New Frontiers in Nucleic Acid Chemistry)
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Open AccessArticle DNA Three Way Junction Core Decorated with Amino Acids-Like Residues-Synthesis and Characterization
Molecules 2016, 21(9), 1082; doi:10.3390/molecules21091082
Received: 5 July 2016 / Revised: 8 August 2016 / Accepted: 10 August 2016 / Published: 23 August 2016
PDF Full-text (1251 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Construction and physico-chemical behavior of DNA three way junction (3WJ) functionalized by protein-like residues (imidazole, alcohol and carboxylic acid) at unpaired positions at the core is described. One 5′-C(S)-propargyl-thymidine nucleotide was specifically incorporated on each strand to react through a post
[...] Read more.
Construction and physico-chemical behavior of DNA three way junction (3WJ) functionalized by protein-like residues (imidazole, alcohol and carboxylic acid) at unpaired positions at the core is described. One 5′-C(S)-propargyl-thymidine nucleotide was specifically incorporated on each strand to react through a post synthetic CuACC reaction with either protected imidazolyl-, hydroxyl- or carboxyl-azide. Structural impacts of 5′-C(S)-functionalization were investigated to evaluate how 3WJ flexibility/stability is affected. Full article
(This article belongs to the collection New Frontiers in Nucleic Acid Chemistry)
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Open AccessArticle Chemical Incorporation of Chain-Terminating Nucleoside Analogs as 3′-Blocking DNA Damage and Their Removal by Human ERCC1-XPF Endonuclease
Molecules 2016, 21(6), 766; doi:10.3390/molecules21060766
Received: 13 May 2016 / Accepted: 3 June 2016 / Published: 11 June 2016
Cited by 1 | PDF Full-text (2286 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Nucleoside/nucleotide analogs that lack the 3′-hydroxy group are widely utilized for HIV therapy. These chain-terminating nucleoside analogs (CTNAs) block DNA synthesis after their incorporation into growing DNA, leading to the antiviral effects. However, they are also considered to be DNA damaging agents, and
[...] Read more.
Nucleoside/nucleotide analogs that lack the 3′-hydroxy group are widely utilized for HIV therapy. These chain-terminating nucleoside analogs (CTNAs) block DNA synthesis after their incorporation into growing DNA, leading to the antiviral effects. However, they are also considered to be DNA damaging agents, and tyrosyl-DNA phosphodiesterase 1, a DNA repair enzyme, is reportedly able to remove such CTNA-modifications of DNA. Here, we have synthesized phosphoramidite building blocks of representative CTNAs, such as acyclovir, abacavir, carbovir, and lamivudine, and oligonucleotides with the 3′-CTNAs were successfully synthesized on solid supports. Using the chemically synthesized oligonucleotides, we investigated the excision of the 3′-CTNAs in DNA by the human excision repair cross complementing protein 1-xeroderma pigmentosum group F (ERCC1-XPF) endonuclease, which is one of the main components of the nucleotide excision repair pathway. A biochemical analysis demonstrated that the ERCC1-XPF endonuclease cleaved 2–7 nt upstream from the 3′-blocking CTNAs, and that DNA synthesis by the Klenow fragment was resumed after the removal of the CTNAs, suggesting that ERCC1-XPF participates in the repair of the CTNA-induced DNA damage. Full article
(This article belongs to the collection New Frontiers in Nucleic Acid Chemistry)
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Open AccessArticle Supramolecular Ring Structures of 7-Methylguanine: A Computational Study of Its Self-assembly and Anion Binding
Molecules 2013, 18(1), 225-235; doi:10.3390/molecules18010225
Received: 1 November 2012 / Revised: 14 December 2012 / Accepted: 21 December 2012 / Published: 27 December 2012
Cited by 1 | PDF Full-text (382 KB)
Abstract
The density functional theory calculations of 7-methylguanine clusters revealed that stable ring assemblies can be formed with or without anions in the center position and hexameric clusters are the most stable and most planar ones. The coordination of anions (Cl, Br
[...] Read more.
The density functional theory calculations of 7-methylguanine clusters revealed that stable ring assemblies can be formed with or without anions in the center position and hexameric clusters are the most stable and most planar ones. The coordination of anions (Cl, Br, NO3) stabilizes and thus favors the formation of planar aggregates. We believe that the predicted planar structures stabilized by anions are good models for self-assembly structures formed at solid-liquid or solid-gas interfaces. Comparing the bonding and average H-bond energy to reference ribbon calculations we pointed out the presence of the previously introduced cooperativity effect in circular supramolecular structures of 7-methylguanine. Full article
(This article belongs to the Special Issue Nucleic Acid Analogs)
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Open AccessArticle 5'-Chloro-5'-deoxy-(±)-ENBA, a Potent and Selective Adenosine A1 Receptor Agonist, Alleviates Neuropathic Pain in Mice Through Functional Glial and Microglial Changes without Affecting Motor or Cardiovascular Functions
Molecules 2012, 17(12), 13712-13726; doi:10.3390/molecules171213712
Received: 12 October 2012 / Revised: 10 November 2012 / Accepted: 13 November 2012 / Published: 22 November 2012
Cited by 16 | PDF Full-text (901 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
This study was undertaken in order to investigate the effect of chronic treatment with 5′-chloro-5′-deoxy-(±)-ENBA, a potent and highly selective agonist of human adenosine A1 receptor, on thermal hyperalgesia and mechanical allodynia in a mouse model of neuropathic pain, the Spared Nerve
[...] Read more.
This study was undertaken in order to investigate the effect of chronic treatment with 5′-chloro-5′-deoxy-(±)-ENBA, a potent and highly selective agonist of human adenosine A1 receptor, on thermal hyperalgesia and mechanical allodynia in a mouse model of neuropathic pain, the Spared Nerve Injury (SNI) of the sciatic nerve. Chronic systemic administration of 5′-chloro-5′-deoxy-(±)-ENBA (0.5 mg/kg, i.p.) reduced both mechanical allodynia and thermal hyperalgesia 3 and 7 days post-SNI, in a way prevented by DPCPX (3 mg/kg, i.p.), a selective A1 adenosine receptor antagonist, without exerting any significant change on the motor coordination or arterial blood pressure. In addition, a single intraperitoneal injection of 5′-chloro-5′-deoxy-(±)-ENBA (0.5 mg/kg, i.p.) 7 days post-SNI also reduced both symptoms for at least two hours. SNI was associated with spinal changes in microglial activation ipsilaterally to the nerve injury. Activated, hypertrophic microglia were significantly reduced by 5′-chloro-5′-deoxy-(±)-ENBA chronic treatment. Our results demonstrated an involvement of adenosine A1 receptor in the amplified nociceptive thresholds and in spinal glial and microglial changes occurred in neuropathic pain, without affecting motor coordination or blood pressure. Our data suggest a possible use of adenosine A1 receptor agonist in neuropathic pain symptoms. Full article
(This article belongs to the Special Issue Nucleic Acid Analogs)
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Open AccessArticle Oligonucleotide-Peptide Conjugates: Solid-Phase Synthesis under Acidic Conditions and Use in ELISA Assays
Molecules 2012, 17(12), 13825-13843; doi:10.3390/molecules171213825
Received: 17 October 2012 / Revised: 16 November 2012 / Accepted: 16 November 2012 / Published: 22 November 2012
Cited by 4 | PDF Full-text (285 KB) | HTML Full-text | XML Full-text
Abstract
Here we used solid-phase methods to prepare oligonucleotides carrying fibrin/ filaggrin citrullinated peptides. Post-synthetic conjugation protocols were successfully applied for the synthesis of oligonucleotides carrying small peptides. A stepwise protocol using acid treatment for the final deprotection allowed the preparation of polypyrimidine oligonucleotides
[...] Read more.
Here we used solid-phase methods to prepare oligonucleotides carrying fibrin/ filaggrin citrullinated peptides. Post-synthetic conjugation protocols were successfully applied for the synthesis of oligonucleotides carrying small peptides. A stepwise protocol using acid treatment for the final deprotection allowed the preparation of polypyrimidine oligonucleotides carrying longer and arginine-rich peptides. An ELISA-based test using the oligonucleotide-citrullinated peptide conjugates was developed for the detection of anti-citrullinated protein/peptide antibodies in human serum from rheumatoid arthritis patients. Full article
(This article belongs to the Special Issue Nucleic Acid Analogs)
Open AccessArticle Endo-S-c-di-GMP Analogues-Polymorphism and Binding Studies with Class I Riboswitch
Molecules 2012, 17(11), 13376-13389; doi:10.3390/molecules171113376
Received: 21 September 2012 / Revised: 30 October 2012 / Accepted: 1 November 2012 / Published: 9 November 2012
Cited by 8 | PDF Full-text (520 KB)
Abstract
C-di-GMP, a cyclic guanine dinucleotide, has been shown to regulate biofilm formation as well as virulence gene expression in a variety of bacteria. Analogues of c-di-GMP have the potential to be used as chemical probes to study c-di-GMP signaling and could even become
[...] Read more.
C-di-GMP, a cyclic guanine dinucleotide, has been shown to regulate biofilm formation as well as virulence gene expression in a variety of bacteria. Analogues of c-di-GMP have the potential to be used as chemical probes to study c-di-GMP signaling and could even become drug leads for the development of anti-biofilm compounds. Herein we report the synthesis and biophysical studies of a series of c-di-GMP analogues, which have both phosphate and sugar moieties simultaneously modified (called endo-S-c-di-GMP analogues). We used computational methods to predict the relative orientation of the guanine nucleobases in c-di-GMP and analogues. DOSY NMR of the endo-S-c-di-GMP series showed that the polymorphism of c-di-GMP can be tuned with conservative modifications to the phosphate and sugar moieties (conformational steering). Binding studies with Vc2 RNA (a class I c-di-GMP riboswitch) revealed that conservative modifications to the phosphate and 2'-positions of c-di-GMP dramatically affected binding to class I riboswitch. Full article
(This article belongs to the Special Issue Nucleic Acid Analogs)
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Open AccessArticle Amplification and Re-Generation of LNA-Modified Libraries
Molecules 2012, 17(11), 13087-13097; doi:10.3390/molecules171113087
Received: 29 September 2012 / Revised: 31 October 2012 / Accepted: 1 November 2012 / Published: 5 November 2012
Cited by 6 | PDF Full-text (505 KB) | HTML Full-text | XML Full-text
Abstract
Locked nucleic acids (LNA) confer high thermal stability and nuclease resistance to oligonucleotides. The discovery of polymerases that accept LNA triphosphates has led us to propose a scheme for the amplification and re-generation of LNA-containing oligonucleotide libraries. Such libraries could be used for
[...] Read more.
Locked nucleic acids (LNA) confer high thermal stability and nuclease resistance to oligonucleotides. The discovery of polymerases that accept LNA triphosphates has led us to propose a scheme for the amplification and re-generation of LNA-containing oligonucleotide libraries. Such libraries could be used for in vitro selection of e.g., native LNA aptamers. We maintained an oligonucleotide library encoding 40 randomized positions with LNA ATP, GTP, CTP, and TTP for 7 rounds of ‘mock’ in vitro selection in the absence of a target and analyzed the sequence composition after rounds 1, 4 and 7. We observed a decrease in LNA-A content from 20.5% in round 1 to 6.6% in round 7. This decrease was accompanied by a substantial bias against successive LNA-As (poly-LNA adenosine tracts) and a relative over-representation of single LNA-As. Maintaining a library with LNA TTP yielded similar results. Together, these results suggest that dispersed LNA monomers are tolerated in our in vitro selection protocol, and that LNA-modified libraries can be sustained for up to at least seven selection rounds, albeit at reduced levels. This enables the discovery of native LNA aptamers and similar oligonucleotide structures. Full article
(This article belongs to the Special Issue Nucleic Acid Analogs)
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Open AccessArticle Synthesis of a Cholesteryl-HEG Phosphoramidite Derivative and Its Application to Lipid-conjugates of the Anti-HIV 5'TGGGAG3' Hotoda’s Sequence
Molecules 2012, 17(10), 12378-12392; doi:10.3390/molecules171012378
Received: 19 September 2012 / Revised: 16 October 2012 / Accepted: 17 October 2012 / Published: 22 October 2012
Cited by 4 | PDF Full-text (316 KB) | HTML Full-text | XML Full-text
Abstract
A novel phosphoramidite derivative of cholesterol, with an ether-linked hexaethylene glycol (HEG) spacer arm, has been obtained through simple and reproducible solid phase modified oligonucleotide synthesis manipulations. This building block and the known phosphoramidite derivative of 3b-(2-hydroxyethoxy)cholesterol have been exploited in standard oligonucleotide
[...] Read more.
A novel phosphoramidite derivative of cholesterol, with an ether-linked hexaethylene glycol (HEG) spacer arm, has been obtained through simple and reproducible solid phase modified oligonucleotide synthesis manipulations. This building block and the known phosphoramidite derivative of 3b-(2-hydroxyethoxy)cholesterol have been exploited in standard oligonucleotide synthesis protocols for the preparation of 5'- conjugates of the G-quadruplex-forming 5'TGGGAG3' oligomer, known as the Hotoda’s sequence, to produce new potential anti-HIV agents. Full article
(This article belongs to the Special Issue Nucleic Acid Analogs)
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Open AccessArticle Acetylated and Methylated β-Cyclodextrins as Viable Soluble Supports for the Synthesis of Short 2′-Oligodeoxyribo-nucleotides in Solution
Molecules 2012, 17(10), 12102-12120; doi:10.3390/molecules171012102
Received: 12 September 2012 / Revised: 12 October 2012 / Accepted: 12 October 2012 / Published: 16 October 2012
Cited by 7 | PDF Full-text (479 KB) | HTML Full-text | XML Full-text
Abstract
Novel soluble supports for oligonucleotide synthesis 11ac have been prepared by immobilizing a 5′-O-protected 3′-O-(hex-5-ynoyl)thymidine (6 or 7) to peracetylated or permethylated 6-deoxy-6-azido-β-cyclodextrins 10a or 10b by Cu(I)-promoted 1,3-dipolar cycloaddition. The applicability of the supports
[...] Read more.
Novel soluble supports for oligonucleotide synthesis 11ac have been prepared by immobilizing a 5′-O-protected 3′-O-(hex-5-ynoyl)thymidine (6 or 7) to peracetylated or permethylated 6-deoxy-6-azido-β-cyclodextrins 10a or 10b by Cu(I)-promoted 1,3-dipolar cycloaddition. The applicability of the supports to oligonucleotide synthesis by the phosphoramidite strategy has been demonstrated by assembling a 3′-TTT-5′ trimer from commercially available 5′-O-(4,4′-dimethoxytrityl)thymidine 3′-phosphoramidite. To simplify the coupling cycle, the 5′-O-(4,4′-dimethoxytrityl) protecting group has been replaced with an acetal that upon acidolytic removal yields volatile products. For this purpose, 5′-O-(1-methoxy-1-methylethyl)-protected 3′-(2-cyanoethyl-N,N-diisopropyl-phosphoramidite)s of thymidine (5a), N4-benzoyl-2′-deoxycytidine (5b) and N6-benzoyl-2′-deoxyadenosine (5c) have been synthesized and utilized in synthesis of a pentameric oligonucleotide 3′-TTCAT-5′ on the permethylated cyclodextrin support 11c. Full article
(This article belongs to the Special Issue Nucleic Acid Analogs)
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Open AccessArticle Synthesis and Photophysical Study of 2′-Deoxyuridines Labeled with Fluorene Derivatives
Molecules 2012, 17(10), 12061-12071; doi:10.3390/molecules171012061
Received: 14 September 2012 / Revised: 3 October 2012 / Accepted: 10 October 2012 / Published: 15 October 2012
Cited by 7 | PDF Full-text (561 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
We examined microenvironment-sensitive fluorescent 2′-deoxyuridines labeled with fluorene derivatives that exhibited solvent-dependent photophysical properties. The high sensitivity of the fluorescence shift and the nucleoside intensity dependence on solvent polarity provided information useful for estimating the polarity of the environment surrounding the fluorescent nucleoside.
[...] Read more.
We examined microenvironment-sensitive fluorescent 2′-deoxyuridines labeled with fluorene derivatives that exhibited solvent-dependent photophysical properties. The high sensitivity of the fluorescence shift and the nucleoside intensity dependence on solvent polarity provided information useful for estimating the polarity of the environment surrounding the fluorescent nucleoside. Full article
(This article belongs to the Special Issue Nucleic Acid Analogs)
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Open AccessArticle Enhancement of Gene Silencing Effect and Membrane Permeability by Peptide-Conjugated 27-Nucleotide Small Interfering RNA
Molecules 2012, 17(9), 11089-11102; doi:10.3390/molecules170911089
Received: 29 August 2012 / Revised: 10 September 2012 / Accepted: 11 September 2012 / Published: 14 September 2012
Cited by 2 | PDF Full-text (484 KB)
Abstract
Two different sizes of siRNAs, of which one type was 21-nucleotide (nt) siRNA containing 2-nt dangling ends and the other type was 27-nt siRNA with blunt ends, were conjugated with a nuclear export signal peptide of HIV-1 Rev at the 5′-sense end. Processing
[...] Read more.
Two different sizes of siRNAs, of which one type was 21-nucleotide (nt) siRNA containing 2-nt dangling ends and the other type was 27-nt siRNA with blunt ends, were conjugated with a nuclear export signal peptide of HIV-1 Rev at the 5′-sense end. Processing by Dicer enzyme, cell membrane permeability, and RNAi efficiency of the peptide-conjugated siRNAs were examined. Dicer cleaved the peptide-conjugated 27-nt siRNA leading to the release of 21-nt siRNA, whereas the peptide-conjugated 21-nt siRNA was not cleaved. High membrane permeability and cytoplasmic localization was found in the conjugates. Moreover, the peptide-conjugated 27-nt siRNA showed increased potency of RNAi in comparison with the nonmodified 21-nt and 27-nt siRNAs, whereas the peptide-conjugated 21-nt siRNA showed decreased RNAi efficacy. This potent RNAi efficacy is probably owing to acceleration of RISC through recognition by Dicer, as well as to the improvement of cell membrane permeability and intracellular accumulation. Full article
(This article belongs to the Special Issue Nucleic Acid Analogs)
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Open AccessArticle Synthesis and Chromatography-Free Purification of PNA-PEO Conjugates for the Functionalisation of Gold Sensors
Molecules 2012, 17(9), 11026-11045; doi:10.3390/molecules170911026
Received: 1 June 2012 / Revised: 30 August 2012 / Accepted: 31 August 2012 / Published: 13 September 2012
Cited by 8 | PDF Full-text (851 KB) | Supplementary Files
Abstract
Peptide Nucleic Acids (PNAs) linked to high molecular weight (MW) poly(ethylene oxide) (PEO) derivatives could be useful conjugates for the direct functionalisation of gold surfaces dedicated to Surface Plasmon Resonance (SPR)-based DNA sensing. However their use is hampered by the difficulty to obtain
[...] Read more.
Peptide Nucleic Acids (PNAs) linked to high molecular weight (MW) poly(ethylene oxide) (PEO) derivatives could be useful conjugates for the direct functionalisation of gold surfaces dedicated to Surface Plasmon Resonance (SPR)-based DNA sensing. However their use is hampered by the difficulty to obtain them through a convenient and economical route. In this work we compared three synthetic strategies to obtain PNA-high MW PEO conjugates composed of (a) a 15-mer PNA sequence as the probe complementary to genomic DNA of Mycobacterium tuberculosis, (b) a PEO moiety (2 or 5 KDa MW) and (c) a terminal trityl-protected thiol necessary (after acidic deprotection) for grafting to gold surfaces. The 15-mer PNA was obtained by solid-phase synthesis. Its amino terminal group was later condensed to bi-functional PEO derivatives (2 and 5 KDa MW) carrying a Trt-cysteine at one end and a carboxyl group at the other end. The reaction was carried out either in solution, using HATU or PyOxim as coupling agents, or through the solid-phase approach, with 49.6%, 100% and 5.2% yield, respectively. A differential solvent extraction strategy for product purification without the need for chromatography is described. The ability of the 5 KDa PEO conjugate to function as a probe for complementary DNA detection was demonstrated using a Grating-Coupling Surface Plasmon Resonance (GC-SPR) system. The optimized PEO conjugation and purification protocols are economical and simple enough to be reproduced also within laboratories that are not highly equipped for chemical synthesis. Full article
(This article belongs to the Special Issue Nucleic Acid Analogs)
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Open AccessArticle Synthesis of Oligonucleotides Carrying Thiol Groups Using a Simple Reagent Derived from Threoninol
Molecules 2012, 17(9), 10026-10045; doi:10.3390/molecules170910026
Received: 27 June 2012 / Revised: 3 August 2012 / Accepted: 14 August 2012 / Published: 24 August 2012
Cited by 3 | PDF Full-text (439 KB) | Supplementary Files
Abstract
Oligonucleotides carrying thiol groups are useful intermediates for a remarkable number of applications involving nucleic acids. In this study, DNA oligonucleotides carrying tert-butylsulfanyl (t-BuS) protected thiol groups have been prepared. A building block derived from threoninol has been developed to
[...] Read more.
Oligonucleotides carrying thiol groups are useful intermediates for a remarkable number of applications involving nucleic acids. In this study, DNA oligonucleotides carrying tert-butylsulfanyl (t-BuS) protected thiol groups have been prepared. A building block derived from threoninol has been developed to introduce a thiol group at any predetemined position of an oligonucleotide. The resulting thiolated oligonucleotides have been used for the preparation of oligonucleotide conjugates and for the functionalization of gold nanoparticles using the reactivity of the thiol groups. Full article
(This article belongs to the Special Issue Nucleic Acid Analogs)
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Open AccessArticle Synthesis, DNA-Binding and Antiproliferative Properties of Acridine and 5-Methylacridine Derivatives
Molecules 2012, 17(6), 7067-7082; doi:10.3390/molecules17067067
Received: 8 May 2012 / Revised: 24 May 2012 / Accepted: 4 June 2012 / Published: 8 June 2012
Cited by 6 | PDF Full-text (395 KB)
Abstract
Several acridine derivatives were synthesized and their anti-proliferative activity was determined. The most active molecules were derivatives of 5-methylacridine-4-carboxylic acid. The DNA binding properties of the synthesized acridines were analyzed by competitive dialysis and compared with the anti-proliferative activities. While inactive acridine derivatives
[...] Read more.
Several acridine derivatives were synthesized and their anti-proliferative activity was determined. The most active molecules were derivatives of 5-methylacridine-4-carboxylic acid. The DNA binding properties of the synthesized acridines were analyzed by competitive dialysis and compared with the anti-proliferative activities. While inactive acridine derivatives showed high selectivity for G-quadruplex structures, the most active 5-methylacridine-4-carboxamide derivatives had high affinity for DNA but showed poor specificity. An NMR titration study was performed with the most active 5-methylacridine-4-carboxamide, confirming the high affinity of this compound for both duplex and quadruplex DNAs. Full article
(This article belongs to the Special Issue Nucleic Acid Analogs)
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Open AccessArticle Development of Diversified Methods for Chemical Modification of the 5,6-Double Bond of Uracil Derivatives Depending on Active Methylene Compounds
Molecules 2012, 17(6), 6519-6546; doi:10.3390/molecules17066519
Received: 28 April 2012 / Revised: 21 May 2012 / Accepted: 21 May 2012 / Published: 30 May 2012
Cited by 2 | PDF Full-text (491 KB)
Abstract
The reaction of 5-halogenouracil and uridine derivatives 1 and 7 with active methylene compounds under basic conditions produced diverse and selective C-C bond formation products by virtue of the nature of the carbanions. Three different types of reactions such as the regioselective C-C
[...] Read more.
The reaction of 5-halogenouracil and uridine derivatives 1 and 7 with active methylene compounds under basic conditions produced diverse and selective C-C bond formation products by virtue of the nature of the carbanions. Three different types of reactions such as the regioselective C-C bond formation at the 5- and 6-positions of uracil and uridine derivatives (products 2, 5, 8, 17, 20 and 21), and the formation of fused heterocycle derivatives 2,4-diazabicyclo[4.1.0]heptane (15) and 2,4-diazabicyclo-[4.1.0]nonane (16) via dual C-C bond formations at both the 5- and 6-positions were due to the different active methylene compounds used as reagents. Full article
(This article belongs to the Special Issue Nucleic Acid Analogs)
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Review

Jump to: Research

Open AccessReview Therapeutic Applications of Nucleic Acids and Their Analogues in Toll-like Receptor Signaling
Molecules 2012, 17(11), 13503-13529; doi:10.3390/molecules171113503
Received: 21 September 2012 / Revised: 7 November 2012 / Accepted: 9 November 2012 / Published: 14 November 2012
Cited by 26 | PDF Full-text (346 KB)
Abstract
Toll-like receptors (TLRs) belong to a family of innate immune receptors that detect and clear invading microbial pathogens. Specifically intracellular TLRs such as TLR3, TLR7, TLR8 and TLR9 recognize nucleic acids such as double-stranded RNA, single-stranded RNA and CpG DNA respectively derived from
[...] Read more.
Toll-like receptors (TLRs) belong to a family of innate immune receptors that detect and clear invading microbial pathogens. Specifically intracellular TLRs such as TLR3, TLR7, TLR8 and TLR9 recognize nucleic acids such as double-stranded RNA, single-stranded RNA and CpG DNA respectively derived from microbial components. Upon infection, nucleic acid sensing TLRs signal within endosomal compartment triggering the induction of essential proinflammatory cytokines and type I interferons to initiate innate immune responses thereby leading to a critical role in the development of adaptive immune responses. Thus, stimulation of TLRs by nucleic acids is a promising area of research for the development of novel therapeutic strategies against pathogenic infection, allergies, malignant neoplasms and autoimmunity. This review summarizes the therapeutic applications of nucleic acids or nucleic acid analogues through the modulation of TLR signaling pathways. Full article
(This article belongs to the Special Issue Nucleic Acid Analogs)
Open AccessReview Structural Probes in Quadruplex Nucleic Acid Structure Determination by NMR
Molecules 2012, 17(11), 13073-13086; doi:10.3390/molecules171113073
Received: 24 September 2012 / Revised: 1 November 2012 / Accepted: 1 November 2012 / Published: 5 November 2012
Cited by 6 | PDF Full-text (418 KB) | HTML Full-text | XML Full-text
Abstract
Traditionally, isotope-labelled DNA and RNA have been fundamental to nucleic acid structural studies by NMR. Four-stranded nucleic acid architectures studies increasingly benefit from a plethora of nucleotide conjugates for resonance assignments, the identification of hydrogen bond alignments, and improving the population of preferred
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Traditionally, isotope-labelled DNA and RNA have been fundamental to nucleic acid structural studies by NMR. Four-stranded nucleic acid architectures studies increasingly benefit from a plethora of nucleotide conjugates for resonance assignments, the identification of hydrogen bond alignments, and improving the population of preferred species within equilibria. In this paper, we review their use for these purposes. Most importantly we identify reasons for the failure of some modifications to result in quadruplex formation. Full article
(This article belongs to the Special Issue Nucleic Acid Analogs)
Open AccessReview Chemical Architecture and Applications of Nucleic Acid Derivatives Containing 1,2,3-Triazole Functionalities Synthesized via Click Chemistry
Molecules 2012, 17(11), 12665-12703; doi:10.3390/molecules171112665
Received: 21 September 2012 / Revised: 19 October 2012 / Accepted: 19 October 2012 / Published: 26 October 2012
Cited by 18 | PDF Full-text (784 KB) | HTML Full-text | XML Full-text
Abstract
There is considerable attention directed at chemically modifying nucleic acids with robust functional groups in order to alter their properties. Since the breakthrough of copper-assisted azide-alkyne cycloadditions (CuAAC), there have been several reports describing the synthesis and properties of novel triazole-modified nucleic acid
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There is considerable attention directed at chemically modifying nucleic acids with robust functional groups in order to alter their properties. Since the breakthrough of copper-assisted azide-alkyne cycloadditions (CuAAC), there have been several reports describing the synthesis and properties of novel triazole-modified nucleic acid derivatives for potential downstream DNA- and RNA-based applications. This review will focus on highlighting representative novel nucleic acid molecular structures that have been synthesized via the “click” azide-alkyne cycloaddition. Many of these derivatives show compatibility for various applications that involve enzymatic transformation, nucleic acid hybridization, molecular tagging and purification, and gene silencing. The details of these applications are discussed. In conclusion, the future of nucleic acid analogues functionalized with triazoles is promising. Full article
(This article belongs to the Special Issue Nucleic Acid Analogs)
Open AccessReview Recent Advances in Cyclonucleosides: C-Cyclonucleosides and Spore Photoproducts in Damaged DNA
Molecules 2012, 17(10), 11630-11654; doi:10.3390/molecules171011630
Received: 30 August 2012 / Revised: 25 September 2012 / Accepted: 26 September 2012 / Published: 28 September 2012
Cited by 4 | PDF Full-text (718 KB)
Abstract
Cyclonucleosides which are fixed in a specific conformation around the glycosyl bond by a carbon and heteroatom chain constitute a unique category of nucleoside derivatives. Because they are structural analogs, cyclonucleosides and oligodeoxynucleotides containing them would be useful tools for investigating the biological
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Cyclonucleosides which are fixed in a specific conformation around the glycosyl bond by a carbon and heteroatom chain constitute a unique category of nucleoside derivatives. Because they are structural analogs, cyclonucleosides and oligodeoxynucleotides containing them would be useful tools for investigating the biological functions and conformations of DNA, RNA as well as their steric interactions with proteins. C-Cyclonucleosides bridged by a carbon chain between the base and sugar moieties are the most attractive from the synthetic points of view as well as for use as biological tools. In this review, recent progress of the synthesis of C-cyclonucleosides is surveyed. Among the C-cyclonucleosides, 5′,8-C-cyclodeoxyadenosine is one of the well-known derivatives of which the first practical synthesis was reported over 30 years ago. Recently, 5′,8-C-cyclodeoxyadenosine has attracted considerable interest as a biomarker, since its formation in oxidatively-damaged DNA is considered to be related to various diseases and aging. Another important analogue of cyclonucleosides is a unique thymidine phosphate dimer, a so-called spore photoproduct, which has been found in photo-damaged DNA. Recent advances in the synthesis, mechanism-studies, and stereochemical preference of repairing enzymes related to 5′,8-C-cyclodeoxyadenosine and spore photoproducts are also reviewed. Full article
(This article belongs to the Special Issue Nucleic Acid Analogs)

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