Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• mannose to PEI via a PEG chain spacer (Figure 3B). This system was used to deliver small interfering RNA (siRNA) into a murine macrophage cell line [44]. Mannose residues as their 2-aminoethyl glycosides were attached by reductive amination to the surface of copolymer micelles of PEG with poly-ε

Streptopyridines, volatile pyridine alkaloids produced by Streptomyces sp. FORM5

• Ulrike Groenhagen,
• Michael Maczka,
• Jeroen S. Dickschat and
• Stefan Schulz

Beilstein J. Org. Chem. 2014, 10, 1421–1432, doi:10.3762/bjoc.10.146

• identification. The streptopyridines showed only weak antibacterial and cytostatic activity (R. Müller, pers. commun.), similar to that described earlier by us for 2-pentylpyridine [31]. The analysis of the 16S-RNA revealed strain FORM5 to be a Streptomyces. It showed 99% sequence similarity to Streptomyces

• synthetic or commercially available reference compound (std). Supporting Information Supporting Information File 102: Total ion chromatograms of strain Streptomyces sp. FORM5, mass spectra, 16S-RNA data, and 1H and 13C NMR spectra of the synthetic compounds. Acknowledgements We thank Silke Wenzel and

• Jennifer Herrmann from the workgroup of Rolf Müller, HIPS, Saarbrücken, Germany, for performing 16S-RNA classification and bioassays. We also thank Axel Zeeck, Göttingen, for the strain FORM5.

Glycosystems in nanotechnology: Gold glyconanoparticles as carrier for anti-HIV prodrugs

• Fabrizio Chiodo,
• Marco Marradi,
• Javier Calvo,
• Eloisa Yuste and
• Soledad Penadés

Beilstein J. Org. Chem. 2014, 10, 1339–1346, doi:10.3762/bjoc.10.136

• triphosphorylated to active metabolites that can compete with the natural substrate of RT avoiding the RNA retrotranscription, e.g., the viral replication. Abacavir and lamivudine (being NRTi) inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator in DNA synthesis. The lack of a 3

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

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

• selective binding with RNA but not with DNA [16][17]. It has been shown that conjugation of PMO with cationic peptides or other cationic residues facilitates penetration of PMO into cells and efficiently prevents the growth of E. coli in vitro and in vivo [18]. Taking the above considerations into account

• was revealed that the MorGly oligomers preferably bind with RNA than with DNA [20]. At the same time, the stability of complementary complexes of modified oligomers was shown to depend on the residues dangling the 4-end of the MorGly oligomers. In this study, the type of the residue dangling the 4-end

• will be used in the further study of the structure and the thermal stability of complementary complexes of the MorGly oligomers with native DNA and RNA to elucidate the role of the hydrogen bonds and base stacking in their formation and stability. The use of highly sophisticated constructs containing

SF002-96-1, a new drimane sesquiterpene lactone from an Aspergillus species, inhibits survivin expression

• Silke Felix,
• Louis P. Sandjo,
• Till Opatz and
• Gerhard Erkel

Beilstein J. Org. Chem. 2013, 9, 2866–2876, doi:10.3762/bjoc.9.323

• highest concentration tested (8 µM). To investigate the effect of the compound on the transcription of the survivin gene, quantitative real-time PCR experiments were performed with total RNA isolated from Colo 320 cells treated with different concentrations of the test compound for 8 h as described in the

The regulation and biosynthesis of antimycins

• Ryan F. Seipke and
• Matthew I. Hutchings

Beilstein J. Org. Chem. 2013, 9, 2556–2563, doi:10.3762/bjoc.9.290

• -aminosalicylate, antCD encode the hybrid NRPS/PKS machinery and antE and antM encode a crotonyl-CoA reductase and a discrete ketoreductase, respectively. The antB and antO genes encode tailoring enzymes and antA encodes an extracytoplasmic function (ECF) RNA polymerase σ factor named σAntA. The additional genes

• genes in stationary phase also suggests that specific regulatory mechanisms must exist to switch off the expression of all four ant operons. Despite this, the 14 ant gene clusters contain only a single conserved regulatory gene, antA, which encodes an orphan ECF RNA polymerase σ factor named σAntA

• , ketosynthase; AT, acyltransferase; ACP, acyl carrier protein; TE, thioesterase; *AntP is a pathway-specific kynureninase that is encoded by L- and I-form ant gene clusters. σAntA comprises a new subfamily of ECF RNA polymerase σ factors. σAntA amino acid sequences were aligned to amino acid sequences of random

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• pyrimidines form very tight hydrogen-bonding arrays as seen in DNA and RNA. Synthetically, the electron-poor nature of pyrimidines accounts for the manifold functionalisation pathways using nucleophilic aromatic substitution chemistry. Electrophilic aromatic substitution reactions are more common during the

Synthesis and antibacterial activity of monocyclic 3-carboxamide tetramic acids

• Yong-Chul Jeong and
• Mark G. Moloney

Beilstein J. Org. Chem. 2013, 9, 1899–1906, doi:10.3762/bjoc.9.224

• inhibitor) [3], R207910 (an ATP synthase inhibitor) [4] and moiramide B (a bacterial acetyl-CoA carboxylase inhibitor) [5]. Both natural 3-acyltetramic acids, for example streptolydigin 1a (bacterial RNA polymerase (RNAP) inhibitory activity) [6] and kibdelomycin 1b (bacterial type II topoisomerase

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• ribonucleic acid polymerase. These compounds inhibit chain initiation of RNA synthesis in Staphylococcus aureus, a particularly infectious bacterial strain with reported drug resistance to the antibiotics vancomycin and methicillin [3]. Ripostatin A exists as an equilibrium mixture of ketone and hemiketal

Recent progress in the discovery of small molecules for the treatment of amyotrophic lateral sclerosis (ALS)

• Allison S. Limpert,
• Margrith E. Mattmann and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2013, 9, 717–732, doi:10.3762/bjoc.9.82

• TARDBP, which encodes for the trans-activating response (TAR) DNA-binding protein 43 (TDP-43), FUS/TLS, which encodes the RNA-binding protein fused in sarcoma, and VAPB, a gene encoding the vesicle-associated membrane-protein-associated protein B/C, and animal models based on mutations in these genes

A new synthetic protocol for coumarin amino acid

• Xinyi Xu,
• Xiaosong Hu and
• Jiangyun Wang

Beilstein J. Org. Chem. 2013, 9, 254–259, doi:10.3762/bjoc.9.30

• Xinyi Xu Xiaosong Hu Jiangyun Wang Laboratory of Noncoding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China Graduate University of the Chinese Academy of Sciences, Beijing 100864, China Department of Chemistry, School of Science, Wuhan University of Technology

Peptoids and polyamines going sweet: Modular synthesis of glycosylated peptoids and polyamines using click chemistry

• Daniel Fürniss,
• Timo Mack,
• Frank Hahn,
• Sidonie B. L. Vollrath,
• Katarzyna Koroniak,
• Ute Schepers and
• Stefan Bräse

Beilstein J. Org. Chem. 2013, 9, 56–63, doi:10.3762/bjoc.9.7

• be efficacious in the cellular delivery of oligonucleotides such as DNA [5][6][7] and RNA [8][9][10][11]. Conjugates of polyamines with aliphatic lipids or cholesterol yielding, i.e., dioctadecylaminoglycylspermine (DOGS, transfectam) are well established reagents for the transfection of DNA and

Chemical modification allows phallotoxins and amatoxins to be used as tools in cell biology

• Jan Anderl,
• Hartmut Echner and
• Heinz Faulstich

Beilstein J. Org. Chem. 2012, 8, 2072–2084, doi:10.3762/bjoc.8.233

• filaments. This interaction is in the nanomolar range and highly specific: no other targets for phalloidin in the cell are known. Amatoxins, such as the main toxin α-amanitin, bind to RNA-polymerases II of eukaryotic cells, thus inhibiting the transcription process at nanomolar concentrations. Also this

• interaction is specific, since RNA-polymerases I are not inhibited at all, whereas RNA-polymerases III are inhibited at amanitin concentrations ca. 1000 times higher than for RNA-polymerases II [2][3]. The fact that both the cytoskeleton and the eukaryotic transcription machine are complex structures and

• stabilizing yeast RNA-polymerase II in an X-ray analysis [7]. For both phallotoxins and amatoxins, experience with live cells is limited by the fact that the peptides cross the plasma membrane barrier only very slowly. Poor uptake rates of phallotoxins and amatoxins have been observed for most mammalian cells

Conformational analysis, stereoelectronic interactions and NMR properties of 2-fluorobicyclo[2.2.1]heptan-7-ols

• Fátima M. P. de Rezende,
• Marilua A. Moreira,
• Rodrigo A. Cormanich and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2012, 8, 1227–1232, doi:10.3762/bjoc.8.137

• exhibits F∙∙∙HO intramolecular HB, is substantially higher, i.e., (−)28.4 Hz [9]. In fact, the importance of NMR scalar spin–spin coupling constants (SSCCs) transmitted through hydrogen bonds emerged, fundamentally, from the observation of 1hJ15N,H and 2hJ15N,15N SSCCs for DNA and RNA molecular systems [10

Parallel solid-phase synthesis of diaryltriazoles

• Matthias Wrobel,
• Jeffrey Aubé and
• Burkhard König

Beilstein J. Org. Chem. 2012, 8, 1027–1036, doi:10.3762/bjoc.8.115

• acids in proteins being part of α-helices [2], it is the most common secondary structure found in proteins [3]. Protein–protein as well as protein–DNA and protein–RNA interactions often involve α-helices as recognition motifs on protein surfaces [4]. These helices are important targets for new drugs

The use of glycoinformatics in glycochemistry

• Thomas Lütteke

Beilstein J. Org. Chem. 2012, 8, 915–929, doi:10.3762/bjoc.8.104

• nucleotides that form DNA or RNA strands [1][2]. Furthermore, the monosaccharides can be linked to each other in several ways, including the possibility to form branched structures. Another important difference between glycans, on the one hand, and proteins and nucleic acids, on the other hand, is visible in

• their biosynthesis: DNA, RNA and proteins are synthesized by copying, transcription or translation, respectively, of nucleic acids, whereas carbohydrates are built in a non-template-driven approach by the sequential action of various glycosyltransferases (GT) that add monosaccharides to an existing

Diarylethene-modified nucleotides for switching optical properties in DNA

• Sebastian Barrois and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2012, 8, 905–914, doi:10.3762/bjoc.8.103

• its planarity and polarity. This assumption was experimentally verified by synthetic spiropyrans as noncovalent DNA and RNA binders [23][24][25]. As expected, ground-state interactions between the noncovalently bound molecular switch and the DNA bases were detected in the case of the merocyanine form

Triterpenoid saponins from the roots of Acanthophyllum gypsophiloides Regel

• Elena A. Khatuntseva,
• Vladimir M. Men’shov,
• Alexander S. Shashkov,
• Yury E. Tsvetkov,
• Rodion N. Stepanenko,
• Raymonda Ya. Vlasenko,
• Elvira E. Shults,
• Genrikh A. Tolstikov,
• Tatjana G. Tolstikova,
• Dimitri S. Baev,
• Vasiliy A. Kaledin,
• Nelli A. Popova,
• Valeriy P. Nikolin,
• Pavel P. Laktionov,
• Anna V. Cherepanova,
• Tatiana V. Kulakovskaya,
• Ekaterina V. Kulakovskaya and
• Nikolay E. Nifantiev

Beilstein J. Org. Chem. 2012, 8, 763–775, doi:10.3762/bjoc.8.87

• cytokines, including IL-6, IL-8 and IL-1β, upon stimulation with bacterial and viral components, such as lipopolysaccharides (LPS) and double-stranded RNA (dsRNA) [25]. HUVEC were cultivated in the presence of saponins 1 and 2 at nontoxic concentrations, i.e., 1 and 5 μg/mL, as determined by EZ4U test, and

Enantioselective supramolecular devices in the gas phase. Resorcin[4]arene as a model system

• Caterina Fraschetti,
• Matthias C. Letzel,
• Antonello Filippi,
• Maurizio Speranza and
• Jochen Mattay

Beilstein J. Org. Chem. 2012, 8, 539–550, doi:10.3762/bjoc.8.62

• are the elementary units of the RNA and DNA biomacromolecules, and their physiological importance at many different levels [52][53][54] makes them potential candidates as anticancer drugs. The gas-phase study of the intimate interactions between the resorcin[4]arene V and several pyrimidine

Multicomponent synthesis of artificial nucleases and their RNase and DNase activity

• Anton V. Gulevich,
• Lyudmila S. Koroleva,
• Olga V. Morozova,
• Valentina N. Bakhvalova,
• Vladimir N. Silnikov and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2011, 7, 1135–1140, doi:10.3762/bjoc.7.131

• activity of the new compounds towards single-stranded RNA and double-stranded circular DNA. Keywords: DNA; isocyanide; multicomponent reaction; organocatalysis; peptidomimetic; RNA; Introduction RNA cleavage can serve as a molecular tool for biological research [1], as well as for development of

• anticancer drugs [2][3] and new therapeutics against RNA-containing viruses. Recently, a number of synthetic RNA-cleaving molecules (artificial ribonucleases) had been developed and tested in vitro [4][5][6][7][8][9][10][11]. Among numerous artificial ribonucleases, peptidomimetics showed evident advantages

• centers of natural RNases A and T1 have been described [13][14][15]. RNA cleavage was shown to be more efficient in the presence of aliphatic hydrophobic linkers [16]. However, the potential role of the alkyl chain of the catalyst remains unclear. Interaction of hydrophobic residues in peptides was

Chiral gold(I) vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor

• María Martín-Rodríguez,
• Carmen Nájera,
• José M. Sansano,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2011, 7, 988–996, doi:10.3762/bjoc.7.111

• ; phosphoramidite; silver; viral inhibitor; Introduction The prevalence of chronic hepatitis C virus (HCV) infection is such that it is estimated to be suffered by around 200 million people worldwide [1]. This enveloped single-stranded RNA virus (belonging to the Flaviviridae family) is present in six major

• as NS2, NS3 (which bear serine proteinase, helicase, and NTPase activities), NS4A, NS4B, NS5A (regulators of RNA replication), and NS5B (the RNA-dependent RNA polymerase) are generated [2][3] and, in fact, constitute the main targets. At the moment, there are many drugs under clinical trial

• inhibit the RNA-dependent RNA polymerase of the virus responsible for hepatitis C (genotype 1g) [5]. Thus, their high replication rates (billions of copies per day) can be drastically suppressed by the inhibition of the NS5B RNA-dependent RNA polymerase enzyme, which is the primary target for oral

Chemical aminoacylation of tRNAs with fluorinated amino acids for in vitro protein mutagenesis

• Shijie Ye,
• Allison Ann Berger,
• Dominique Petzold,
• Oliver Reimann,
• Benjamin Matt and
• Beate Koksch

Beilstein J. Org. Chem. 2010, 6, No. 40, doi:10.3762/bjoc.6.40

• ][25][26][27]. We chose a combination of chemical and enzymatic aminoacylation which relies on the hybrid dinucleotide pdCpA and the T4-RNA ligase-mediated coupling to it to give a truncated suppressor tRNA. The Nα-amino groups of the amino acids were protected with the 4-pentenoyl group and the amino

• and incorporated into proteins [29][30]. pdCpA bearing Abu or the fluorinated amino acid analogue were efficiently ligated to the truncated suppressor tRNAPheCUA by treatment with T4-RNA ligase and were analyzed using denatured acidic PAGE (Figure 3) [31]. Thus, both our mono- and bis-acylated tRNAs

• . (RS)-2-amino-2-methyl-3,3,3-trifluoropropanoic acid. Denaturing PAGE of ligation products of truncated suppressor tRNA and fluorinated aminoacyl-pdCpAs and Abu-pdCpA. Lane 1: RNA Marker 100 bp, Lane 2: transcribed full-length tRNACUA, Lane 3: transcribed truncated tRNACUA-COH, Lane 4: Abu-tRNACUA

(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

• other, a high degree of diversity can be achieved by employing only a small set of different SDAs. Moreover, oligomeric SDAs with unprotected groups represent a novel type of aminoglycoside mimetics with potential recognition properties towards new RNA targets emerging in the post-genome era. Cyclic SAA

• negatively charged functional groups such as phosphate or carboxylate groups in DNA, RNA and proteins. Tóth and co-workers [90] synthesised a series of guanidine-linked sugars as a new class of oligosaccharide mimics to study their interactions with proteins. Thus, reaction of the carbodiimide-linked

• [83][84]. Numerous structural analogues of DNA/RNA designed to be effective antisense/antigene agents have been reported. An interesting approach involves replacing the negatively charged phosphodiester linkages of RNA/DNA by positively charged guanidinium linkages. The guanidinium linkage is

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

• channel structure with 4,4'-bipyridyl. [5] Although hydrogen bonding aspects of cyanuric acid have been studied in detail, similar structures formed by uracil possessing two imide groups has not been studied adequately, except for its hydrogen bonding with adenine in RNA. [6] In RNA, uracil forms cyclic