Special Issue "Nucleic Acid Analogs"

Guest Editor
Prof. Dr. Lajos Kovacs
Nucleic Acids Laboratory, Department of Medicinal Chemistry, Universtiy of Szeged, Dóm tér 8, H-6720 Szeged, Hungary
Website: http://www.mdche.u-szeged.hu/~kovacs/nal.html
E-Mail: kovacs.lajos@med.u-szeged.hu
Phone: +36 62 54 51 45
Fax: +36 62 42 59 71
Interests: preparative organic chemistry of carbohydrates; nucleobases; nucleosides; C-nucleosides; peptide nucleic acids; indoles; alkaloids; polyamines; heterocycles; protecting groups; chemical information management

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

Submission

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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

Hironao Sajiki, Yusuke Iida, Kanoko Ikawa, Yoshinari Sawama, Yasunari Monguchi, Yukio Kitade, Yoshifumi Maki, Hideo Inoue and Kosaku Hirota Article: 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; in revised form: 21 May 2012 / Accepted: 21 May 2012 / Published: 30 May 2012 Show/Hide Abstract | Download 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 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.

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Rubén Ferreira, Anna Aviñó, Stefania Mazzini and Ramon Eritja Article: 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; in revised form: 24 May 2012 / Accepted: 4 June 2012 / Published: 8 June 2012 Show/Hide Abstract | Download 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 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.

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Sonia Pérez-Rentero, Santiago Grijalvo, Rubén Ferreira and Ramon Eritja Article: 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; in revised form: 3 August 2012 / Accepted: 14 August 2012 / Published: 24 August 2012 Show/Hide Abstract | Download PDF Full-text (439 KB) |  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 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.

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Monica Dettin, Davide Silvestri, Roberta Danesin, Erica Cretaio, Gianluca Picariello, Elisabetta Casarin, Agnese Sonato, Filippo Romanato and Margherita Morpurgo Article: 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; in revised form: 30 August 2012 / Accepted: 31 August 2012 / Published: 13 September 2012 Show/Hide Abstract | Download PDF Full-text (851 KB) |  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 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.

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Takanori Kubo, Kazuyoshi Yanagihara, Yuichiro Sato, Yasuhiro Morita and Toshio Seyama Article: 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; in revised form: 10 September 2012 / Accepted: 11 September 2012 / Published: 14 September 2012 Show/Hide Abstract | Download 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 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.

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Yuichi Yoshimura and Hiroki Takahata Review: 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; in revised form: 25 September 2012 / Accepted: 26 September 2012 / Published: 28 September 2012 Show/Hide Abstract | Download 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 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.

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Hyun Yi Cho, Sang Keun Woo and Gil Tae Hwang Article: 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; in revised form: 3 October 2012 / Accepted: 10 October 2012 / Published: 15 October 2012 Show/Hide Abstract | Download PDF Full-text (561 KB) | Download XML Full-text |  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.

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Alejandro Gimenez Molina, Vyacheslav Kungurtsev, Pasi Virta and Harri Lönnberg Article: 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; in revised form: 12 October 2012 / Accepted: 12 October 2012 / Published: 16 October 2012 Show/Hide Abstract | Download PDF Full-text (479 KB) | Download XML Full-text Abstract: Novel soluble supports for oligonucleotide synthesis 11a–c 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.

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Domenica Musumeci and Daniela Montesarchio Article: 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; in revised form: 16 October 2012 / Accepted: 17 October 2012 / Published: 22 October 2012 Show/Hide Abstract | Download PDF Full-text (316 KB) | Download 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 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.

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Tim Efthymiou, Wei Gong and Jean-Paul Desaulniers Review: 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; in revised form: 19 October 2012 / Accepted: 19 October 2012 / Published: 26 October 2012 Show/Hide Abstract | Download PDF Full-text (784 KB) | Download 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 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.

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Andreas Ioannis Karsisiotis and Mateus Webba da Silva Review: Structural Probes in Quadruplex Nucleic Acid Structure Determination by NMR Molecules 2012, 17(11), 13073-13086; doi:10.3390/molecules171113073 Received: 24 September 2012; in revised form: 1 November 2012 / Accepted: 1 November 2012 / Published: 5 November 2012 Show/Hide Abstract | Download PDF Full-text (418 KB) | Download 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 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.

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Holger Doessing, Lykke H. Hansen, Rakesh N. Veedu, Jesper Wengel and Birte Vester Article: Amplification and Re-Generation of LNA-Modified Libraries Molecules 2012, 17(11), 13087-13097; doi:10.3390/molecules171113087 Received: 29 September 2012; in revised form: 31 October 2012 / Accepted: 1 November 2012 / Published: 5 November 2012 Show/Hide Abstract | Download PDF Full-text (505 KB) | Download 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 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.

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Jie Zhou, David A. Sayre, Jingxin Wang, Nirmal Pahadi and Herman O. Sintim Article: 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; in revised form: 30 October 2012 / Accepted: 1 November 2012 / Published: 9 November 2012 Show/Hide Abstract | Download 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 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.

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Vijayakumar Gosu, Shaherin Basith, O-Pil Kwon and Sangdun Choi Review: 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; in revised form: 7 November 2012 / Accepted: 9 November 2012 / Published: 14 November 2012 Show/Hide Abstract | Download 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 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.

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Livio Luongo, Riccardo Petrelli, Luisa Gatta, Catia Giordano, Francesca Guida, Patrizia Vita, Palmarisa Franchetti, Mario Grifantini, Vito de Novellis, Loredana Cappellacci and Sabatino Maione Article: 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; in revised form: 10 November 2012 / Accepted: 13 November 2012 / Published: 22 November 2012 Show/Hide Abstract | Download PDF Full-text (901 KB) | Download XML Full-text |  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 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.

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Anna Aviñó, Maria José Gómara, Morteza Malakoutikhah, Isabel Haro and Ramon Eritja Article: 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; in revised form: 16 November 2012 / Accepted: 16 November 2012 / Published: 22 November 2012 Show/Hide Abstract | Download PDF Full-text (285 KB) | Download 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 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.

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Gábor Paragi, Zoltán Kupihár, Célia Fonseca Guerra, F. Matthias Bickelhaupt and Lajos Kovács Article: 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; in revised form: 14 December 2012 / Accepted: 21 December 2012 / Published: 27 December 2012 Show/Hide Abstract | Download 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−, 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.

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Type of Paper: Article
Title: Synthesis of Oligonucleotides Carrying Thiol Groups Using a Simple Reagent Derived from Threoninol
Authors: Sónia Pérez-Rentero, Santiago Grijalvo, Rubén Ferreira and RamonEritja
Affiliations: Institute for Research in Biomedicine (IRB Barcelona), Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Networking Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Baldiri Reixac 10, E-08028 Barcelona, Spain
Abstract: Oligonucleotides carrying thiol groups are important intermediates for the preparation of oligonucleotide conjugates and for the functionalization of nanomaterials. In this paper, DNA oligonucleotides carrying tert-butylsulfanyl (tBuS) 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 thiol-oligonucleotides was used for the introduction of fluorescent dyes with excellent yields.

Type of Paper: Review
Title: Chemical Architecture and Applications of Nucleic Acid Derivatives that Contain Triazole Functionalities
Authors: Tim C. Efthymiou, Wei Gong and Jean-Paul Desaulniers
Affiliations: University of Ontario Institute of Technology, Oshawa, ON L1H 7K4, Canada
Abstract: There is considerable attention directed at chemically modifying nucleic acids with robust functional groups in order to alter its properties. Since the breakthrough of copper-assisted 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 an 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 analogs functionalized with triazoles is promising.