Synthesis of novel conjugates of a saccharide, amino acids, nucleobase and the evaluation of their cell compatibility

• Dan Yuan,
• Xuewen Du,
• Junfeng Shi,
• Ning Zhou,
• Abdulgader Ahmed Baoum and
• Bing Xu

Beilstein J. Org. Chem. 2014, 10, 2406–2413, doi:10.3762/bjoc.10.250

• synthesis of a novel type of conjugate of three fundamental biological build blocks (i.e., saccharide, amino acids, and nucleobase) and their cell compatibility. The facile synthesis starts with the synthesis of nucleobase and saccharide derivatives, then uses solid-phase peptide synthesis (SPPS) to build

• conjugates of saccharide–amino acids–nucleobase (SAN), like the previously reported conjugates of nucleobase–amino acids–saccharide (NAS) and nucleobase–saccharide–amino acids (NSA), are mammalian cell compatible. Keywords: cell compatibility; nucleobase; peptides; saccharide; Introduction As a result of

• types of building blocks for generating supramolecular nanofibers in water [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15]. Recently, we have demonstrated that not only the conjugates of nucleobase–amino acids–saccharide (NAS) [16][17][18] but also the conjugates of nucleobase–saccharide–amino acids

Autonomous assembly of synthetic oligonucleotides built from an expanded DNA alphabet. Total synthesis of a gene encoding kanamycin resistance

• Kristen K. Merritt,
• Kevin M. Bradley,
• Daniel Hutter,
• Mariko F. Matsuura,
• Diane J. Rowold and
• Steven A. Benner

Beilstein J. Org. Chem. 2014, 10, 2348–2360, doi:10.3762/bjoc.10.245

• long DNA (L-DNA) constructs from short synthetic DNA fragments, which are today quite inexpensive because of automated solid-phase synthesis. However, the low information density of DNA built from just four nucleotide “letters”, the presence of strong (G:C) and weak (A:T) nucleobase pairs, the non

• technology to assemble single-stranded synthetic fragments to give 20,000 base-pair DNA constructs. If DNA were in fact the idealized molecule taught in introductory biochemistry classes, the specificity of Watson–Crick nucleobase pairing might indeed allow autonomous assembly of large numbers of synthetic

• accommodating another weak nucleobase pair. Further, S and B can be used strategically, as illustrated in the synthesis of the kanamycin gene. Here, S and B were placed at the ends of the single-stranded oligonucleotides, and not in the central portions of those oligonucleotides. This makes it essentially

Reversibly locked thionucleobase pairs in DNA to study base flipping enzymes

• Christine Beuck and
• Elmar Weinhold

Beilstein J. Org. Chem. 2014, 10, 2293–2306, doi:10.3762/bjoc.10.239

• ][45][46][47][48]. The amino-alkylthiol linker is introduced as its disulfide dimer to protect the sulfur and ensure that the reaction with the convertible nucleobase occurs via the amino group. Two of these residues are placed in adjacent base pairs and reduction of the linker disulfides frees the

• 1I6S-Et-S4U2 and 1G6S-Et-S4U2 clearly confirms the shift of the thio-nucleobase absorption band over 300 nm towards lower wavelengths as it is typical for S-alkylated thio-nucleobases (Figure 2c and Figure 3c). Circular dichroism [53] spectroscopy is sensitive to the overall global conformation of

• . Many other proteins locally open up the DNA duplex to perform their function, ranging from flipping a single nucleobase out of the DNA helix to melting whole stretches of base pairs. A base flipping mechanism is utilized by many enzymes that either chemically modify the flipped nucleobase or repair a

Molecular recognition of AT-DNA sequences by the induced CD pattern of dibenzotetraaza[14]annulene (DBTAA)–adenine derivatives

• Marijana Radić Stojković,
• Marko Škugor,
• Łukasz Dudek,
• Jarosław Grolik,
• Julita Eilmes and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2175–2185, doi:10.3762/bjoc.10.225

• advantage of nucleobase incorporation in small molecule structures for the recognition of complementary nucleotides/polynucleotides [8][9][10]. Recent studies of the novel DBTAA-adenine conjugates AP3 and AP6 (Scheme 1) showed a highly selective binding of only AP3 to poly dT among all other ss-DNA/RNA, as

Synthesis and optical properties of pyrrolidinyl peptide nucleic acid carrying a clicked Nile red label

• Nattawut Yotapan,
• Chayan Charoenpakdee,
• Pawinee Wathanathavorn,
• Boonsong Ditmangklo,
• Hans-Achim Wagenknecht and
• Tirayut Vilaivan

Beilstein J. Org. Chem. 2014, 10, 2166–2174, doi:10.3762/bjoc.10.224

• completion of the synthesis, the N-terminal Fmoc group was removed and the free amino group was capped by acetylation. The acpcPNA on the solid support was spilt to 0.5 µmol portions for a further labeling experiment and treated with 1:1 dioxane/aqueous NH3 at 60 °C overnight to remove the nucleobase- and

Synthesis of phosphoramidites of isoGNA, an isomer of glycerol nucleic acid

• Keunsoo Kim,
• Venkateshwarlu Punna,
• Phaneendrasai Karri and
• Ramanarayanan Krishnamurthy

Beilstein J. Org. Chem. 2014, 10, 2131–2138, doi:10.3762/bjoc.10.220

• known [10][11][12][13][14][15], the published synthetic routes and efficiencies of these vary widely and primarily depend on the nature of the nucleobase. Herein, we detail our synthetic efforts and the current improvements for the synthesis of all four isoGNA nucleosides and their phosphoramidites

Pyrrolidine nucleotide analogs with a tunable conformation

• Lenka Poštová Slavětínská,
• Dominik Rejman and
• Radek Pohl

Beilstein J. Org. Chem. 2014, 10, 1967–1980, doi:10.3762/bjoc.10.205

• 7–14 were investigated by means of NMR and molecular modeling. The effect of the relative configuration of hydroxy and nucleobase substituents as well as the effect of the alkylation or acylation of the pyrrolidine nitrogen atom on the conformation of the pyrrolidine ring were studied. The results

• and H,C-HMBC experiments (for a complete signal assignment and copies of NMR spectra, see Supporting Information File 1). The numbering of the pyrrolidine ring, the nucleobase and the endocyclic phase angles Φ0–Φ4 for the purposes of the conformational analysis is shown in Figure 3. There are

• , which indicates that isolated compounds are in the form of the monosodium monozwitterionic salt. The orientation of the phosphonomethyl moiety relative to the nucleobase in the zwitterionic form could be theoretically deduced from the H,H-ROESY spectra. In real spectra, however, protons from CH2PO(OH)2

Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

• Mahesh K. Lakshman,
• Manish K. Singh,
• Mukesh Kumar,
• Raghu Ram Chamala,
• Vijayender R. Yedulla,
• Domenick Wagner,
• Evan Leung,
• Lijia Yang,
• Asha Matin and
• Sadia Ahmad

Beilstein J. Org. Chem. 2014, 10, 1919–1932, doi:10.3762/bjoc.10.200

• nucleobase, we first considered synthesis of nucleoside-like entities (Scheme 5). In this context, N-alkylbenzotriazolyl derivatives and ribonucleoside analogues containing a benzotriazole as a nucleobase surrogate have shown interesting activities towards NTPase/helicase of Flaviviridae viruses [1][2

• benzo- and azabenzotriazole as a nucleobase surrogate have been synthesized. Because benzotriazole derivatives have potentially important pharmacological applications, we anticipate expansion of this chemistry in the future to a broader range of nucleoside-like entities for biological assays. The

Syntheses of ¹⁵N-labeled pre-queuosine nucleobase derivatives

• Jasmin Levic and
• Ronald Micura

Beilstein J. Org. Chem. 2014, 10, 1914–1918, doi:10.3762/bjoc.10.199

• biosynthetic pathway of the hypermodified tRNA nucleoside queuosine [3]. Recently, preQ1 base has attracted considerable attention because this nucleobase specifically binds to bacterial mRNA domains and regulates genes that are required for queuosine biosynthesis, by a so-called riboswitch mechanism [4][5][6

Synthesis of a bifunctional cytidine derivative and its conjugation to RNA for in vitro selection of a cytidine deaminase ribozyme

• Nico Rublack and
• Sabine Müller

Beilstein J. Org. Chem. 2014, 10, 1906–1913, doi:10.3762/bjoc.10.198

• . In terms of synthesis efficiency, we first tried to simultaneously deprotect the amino functionality at the nucleobase and the sugar 5'-hydroxy group to generate derivative 12. Thereafter, the greater nucleophilicity of the primary amine over the alcohol should be used for selective amide bond

• . Two linker moieties of different lengths and functionality were attached to the nucleobase and to the sugar residue of cytidine, thus enabling for one coupling of the nucleoside to periodate-oxidized RNAs, and for second linking the functionalized library to a surface. The 5'-O-coupled linker carrying

• an aliphatic amino group allows 3'-terminal conjugation of cytidine to the molecules of an RNA library, whereas the biotinylated linker attached to C4 of the nucleobase allows linking the modified library to a streptavidine coated surface. The suitability of the synthesized cytidine derivative was

Structure/affinity studies in the bicyclo-DNA series: Synthesis and properties of oligonucleotides containing bc^en-T and iso-tricyclo-T nucleosides

• Branislav Dugovic,
• Michael Wagner and
• Christian J. Leumann

Beilstein J. Org. Chem. 2014, 10, 1840–1847, doi:10.3762/bjoc.10.194

• use of compound 6 as nucleobase acceptor improved the yield of nucleosides 7α,β in general and led to an acceptable β:α = 2.5:1 ratio of anomers. Subsequent saponification of 7α,β (unseparable by flash chromatography) proved to be tricky and after testing a series of standard techniques, only

OligArch: A software tool to allow artificially expanded genetic information systems (AEGIS) to guide the autonomous self-assembly of long DNA constructs from multiple DNA single strands

• Kevin M. Bradley and
• Steven A. Benner

Beilstein J. Org. Chem. 2014, 10, 1826–1833, doi:10.3762/bjoc.10.192

• nucleobase pairing might indeed allow autonomous self-assembly of an unlimited number of DNA strands to give L-DNA constructs of indefinitely large lengths. All that would be necessary is to design the requisite number of synthetic single strand fragments to remove off-target annealing, make them, and mix

• genetic information system (AEGIS) [3][9]. AEGIS adds nucleotide building blocks to the four found in standard DNA (G, A, C, and T) by shuffling hydrogen-bonding units on the nucleobases, all while retaining the overall Watson–Crick nucleobase pairing geometry (Figure 2). These extra nucleotides bind to

• form additional nucleobase pairs orthogonally to the A:T and G:C pairs. In principle, adding extra nucleotides in the genetic alphabet can mitigate the hybridization problems in highly complex mixtures of single-strand DNA fragments simply by increasing the information density of the resulting DNA

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• comparison to ulodesine 19a, compound (3S,4S)-23 exhibited decreased oral availability in mice (0.2 mg/kg dose) and lower duration of action. Compounds 25 and 26, prepared by Chen et al. [71], can be considered as analogs of reversed nucleosides [72] with the thiazolidin-4-one mimic of a nucleobase (Scheme

• asymmetric Biginelli reaction have been reviewed [97]. The reaction has been employed in the synthesis of C-nucleosides with 3,4-dihydropyrimidin-2(1H)-one or 3,4-dihydropyrimidin-2(1H)-thione as the nucleobase mimic. Up to date, depending on the role of the carbohydrate component in the reaction, C

• -nucleosides bearing the carbohydrate moiety at the position of N-1, C-4 or C-6 of the nucleobase mimic were synthesized. Starting from sugar aldehyde substrates 73, Molina et al. synthesized a series of compounds 74 bearing the carbohydrate moiety at the C-4 carbon atom of the 3,4-dihydropyrimidin-2(1H)-one

Pyrene-modified PNAs: Stacking interactions and selective excimer emission in PNA₂DNA triplexes

• Alex Manicardi,
• Lucia Guidi,
• Alice Ghidini and
• Roberto Corradini

Beilstein J. Org. Chem. 2014, 10, 1495–1503, doi:10.3762/bjoc.10.154

• positioning of the pyrene units along the chain. An increase in triplex stability and a very high mismatch-selectivity, derived from combined stacking and base-pairing interactions, were found for PNA2, bearing two distant pyrene units. Keywords: modified nucleobase; nucleic acids; PNA; pyrene excimer; SNP

• ), probably due to the quenching effect of nucleobase units; however, the most important data are related to changes in the fluorescence spectrum upon hybridization with DNA, since this property is strongly related to the environment around the fluorophores [38] and can reveal interactions between pyrene

• (which has the same position as in PNA1), stabilizes the triplex structure through the occurrence of combined stacking interactions (Figure 3b). Thus, the presence of a single mismatch facing the central modified monomer results in destabilization not only of the excimer corresponding to this nucleobase

Solid-phase-supported synthesis of morpholinoglycine oligonucleotide mimics

• Tatyana V. Abramova,
• Sergey S. Belov,
• Yulia V. Tarasenko and
• Vladimir N. Silnikov

Beilstein J. Org. Chem. 2014, 10, 1151–1158, doi:10.3762/bjoc.10.115

• stability was higher for modified oligomers than for native oligodeoxyriboadenylates. This result may indicate that the contribution of nucleobase stacking to the thermal stability of complementary complexes is more important for the oligonucleotide mimics than for native oligonucleotides. The substitution

A new building block for DNA network formation by self-assembly and polymerase chain reaction

• Holger Bußkamp,
• Sascha Keller,
• Marta Robotta,
• Malte Drescher and
• Andreas Marx

Beilstein J. Org. Chem. 2014, 10, 1037–1046, doi:10.3762/bjoc.10.104

• developed covalently connected, 3-armed bDNA constructs (Y-motif) that act as primer and reverse primer strands in PCR [38][39][40]. The branching of the DNA was realized via a flexible alkyl chain that was connected to the nucleobase. Although the primer strands were covalently connected, they were

Synthesis of novel derivatives of 5-hydroxymethylcytosine and 5-formylcytosine as tools for epigenetics

• Anna Chentsova,
• Era Kapourani and
• Athanassios Giannis

Beilstein J. Org. Chem. 2014, 10, 7–11, doi:10.3762/bjoc.10.2

• of the TCBoc group afforded derivatives 9a–d. These new nucleobase modified 2’-deoxycytidine analogues can be used in the synthesis [29][33][34] of modified DNA oligomers for further studies of the TET-mediated processes which are of great importance in the emerging field of epigenetics. In addition

Synthesis of nucleotide–amino acid conjugates designed for photo-CIDNP experiments by a phosphotriester approach

• Tatyana V. Abramova,
• Olga B. Morozova,
• Vladimir N. Silnikov and
• Alexandra V. Yurkovskaya

Beilstein J. Org. Chem. 2013, 9, 2898–2909, doi:10.3762/bjoc.9.326

• linker group between the amino acid and nucleoside residues to avoid this problem. Phosphodiester linkages in conjugates 1–8 are stable in a wide pH range. Conjugates 4 and 5 containing no guanine nucleobase are control compounds for conjugates 2 and 3, respectively. Preliminary results revealed a rapid

• ’-monophosphate (5.40 g, 12.0 mmol) was obtained as a cream-coloured powder. Before the next step (protection of the 3’-OH group by the levulinyl residue), the nucleotide with the protected nucleobase was converted to the TEA salt by adding TEA (5 mL, 35 mmol) to its solution in 50% aqueous Py (50 mL

• with a linear gradient of NH4HCO3 (0–0.5 M) in 20% aqueous EtOH. The appropriate fractions were pooled and evaporated. Nucleobase deprotection and the subsequent purification by RPC were performed as described for conjugate 1. After drying, 0.06 g of conjugate 6 (0.09 mmol, 50% calcd to 15 taken into

Synthesis of trifunctional cyclo-β-tripeptide templates

• Frank Stein,
• Tahir Mehmood,
• Tilman Plass,
• Javid H. Zaidi and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2012, 8, 1576–1583, doi:10.3762/bjoc.8.180

• reported, as well as the functionalization with the nucleobase recognition units thymine-1-yl acetic acid (6) and (N4-benzyloxycarbonyl)cytosine-1-yl acetic acid (7) (Figure 3). In all cases, the template contains a third option for functionalization by covalent attachment of molecules through [3+2

• (5) and the nucleobase moieties thymine-1-yl acetic acid (6) and (N4-benzyloxycarbonyl)cytosine-1-yl acetic acid (7) were attached to the cyclo-β-peptide yielding monofunctionalized templates 14, 10 and 12 (Figure 4). The second amino group was Fmoc-deprotected with 20% piperidine in DMF. Coupling of

Selectivity in C-alkylation of dianions of protected 6-methyluridine

• Ngoc Hoa Nguyen,
• Christophe Len,
• Anne-Sophie Castanet and
• Jacques Mortier

Beilstein J. Org. Chem. 2011, 7, 1228–1233, doi:10.3762/bjoc.7.143

• -alkenyluridines; Introduction Conformationally restricted C–C bridged cyclonucleosides bearing a linkage between the sugar moiety and the nucleobase, exhibit a broad spectrum of antiviral and antitumor activities [1][2][3][4]. Cyclonucleosides are excellent tools for studying the role of the conformational

Synthesis of some novel hydrazono acyclic nucleoside analogues

• Mohammad N. Soltani Rad,
• Ali Khalafi-Nezhad and
• Somayeh Behrouz

Beilstein J. Org. Chem. 2010, 6, No. 49, doi:10.3762/bjoc.6.49

• of ketones 1h–1o In a two-neck round-bottom flask (100 mL) equipped with a condenser, a mixture of the appropriate nucleobase (0.01 mol), the 2-bromoacetophenone (0.012 mol), K2CO3 (1.38 g, 0.01 mol) and a catalytic amount of TBAB (0.1 g) was dissolved in dry DMF (30 mL). The mixture was then heated

Symmetrical and unsymmetrical α,ω-nucleobase amide-conjugated systems

• Sławomir Boncel,
• Maciej Mączka,
• Krzysztof K. K. Koziol,
• Radosław Motyka and
• Krzysztof Z. Walczak

Beilstein J. Org. Chem. 2010, 6, No. 34, doi:10.3762/bjoc.6.34

• , Department of Materials Science and Metallurgy, Pembroke Street, Cambridge CB2 3QZ, United Kingdom, Tel.: +44 1223 334 356, Fax: +44 1223 334 567 10.3762/bjoc.6.34 Abstract We present the synthesis and selected physicochemical properties of several novel symmetrical and unsymmetrical α,ω-nucleobase mono

• nanofibres. Keywords: amides; antiprotozoal agents; coupling; nucleosides; self-assembly; Introduction There are numerous reports on the synthesis and application of symmetrical and unsymmetrical α,ω-nucleobase amide-conjugated systems (Figure 1) [1][2][3][4][5][6]. These molecules are constructed usually

• ]. Moreover, α,ω-nucleobase amide-conjugated molecules possess the tendency to form meta-stable complexes with DNA and thus can perturb the cell replication. For example, amide-linked heterodimer synthons consisting of acyclic nucleoside units and 5′-amino-2′,5′-dideoxythymidine are PNA/DNA chimeras (V) [4

(Pseudo)amide-linked oligosaccharide mimetics: molecular recognition and supramolecular properties

• José L. Jiménez Blanco,
• Fernando Ortega-Caballero,
• Carmen Ortiz Mellet and
• José M. García Fernández

Beilstein J. Org. Chem. 2010, 6, No. 20, doi:10.3762/bjoc.6.20

• -deazaguanine (c7G), forms a 1:1 complex with pentameric adenyl DNA. Deazaguanine nucleobase was chosen because of the unique glycoside bond stability and its ability to prevent G-quartet formation. To increase the already strong binding of DNG to DNA, DNG was combined with a ligand capable of binding

A hydrogen- bonded channel structure formed by a complex of uracil and melamine

• Reji Thomas and
• G. U. Kulkarni

Beilstein J. Org. Chem. 2007, 3, No. 17, doi:10.1186/1860-5397-3-17

• different, in shape and dimension. This clearly indicates the role of the uracil molecule in directing the shape of the channel structure. In conclusion, we have illustrated the molecular recognition process of melamine with nucleobase uracil. We have also established the presence of channels, in the three

Synthesis of coumarin or ferrocene labeled nucleosides via Staudinger ligation

• Ivana Kosiova,
• Andrea Janicova and
• Pavol Kois

Beilstein J. Org. Chem. 2006, 2, No. 23, doi:10.1186/1860-5397-2-23

• . The structure of products 13a-c was confirmed by 1H NMR analysis. The ratio of product and 4-methyl derivative is probably influenced by diverse effects of nucleobase on the reaction mechanism, especially the interaction of nucleobases with triphenylphosphine residue in the intermediates I(a-c)-IV(a-c