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

• biologists to engineer optimally self-assembling DNA constructs from both six- and eight-letter AEGIS alphabets. This software has been used to design oligonucleotides that self-assemble to form complete genes from 20 or more single-stranded synthetic oligonucleotides. OligArch is therefore a key element of

• development of "synthetic biology“ as a modern field over the past 30 years [1][2][3][4][5]. While oligonucleotides can be reliably prepared by automated synthesis up to ca. 100 nucleotides in length and (even today) are most often used as primers, many seek to create large DNA (L-DNA) constructs by assembly

• assembly typically failed between 16 and 24 oligonucleotides. Other methods of assembly, such as the Gibson Assembly [7] or SLIC [8], either limit the number of fragments to be used or rely on stepwise assembly of such syntheses, with the recommendation from Gibson that autonomous self-assembly of single

The chemoenzymatic synthesis of clofarabine and related 2′-deoxyfluoroarabinosyl nucleosides: the electronic and stereochemical factors determining substrate recognition by E. coli nucleoside phosphorylases

• Ilja V. Fateev,
• Konstantin V. Antonov,
• Irina D. Konstantinova,
• Tatyana I. Muravyova,
• Frank Seela,
• Roman S. Esipov,
• Anatoly I. Miroshnikov and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2014, 10, 1657–1669, doi:10.3762/bjoc.10.173

• ; Introduction Pyrimidine and purine 2-deoxy-2-fluoro-β-D-arabinofuranosides demonstrate a broad spectrum of biological activity [1][2][3][4][5][6][7][8][9] and are valuable constituents of artificial oligonucleotides of great molecular biological and medicinal potential [10][11]. Among this family of

Influence of perylenediimide–pyrene supramolecular interactions on the stability of DNA-based hybrids: Importance of electrostatic complementarity

• Christian B. Winiger,
• Simon M. Langenegger,
• Oleg Khorev and
• Robert Häner

Beilstein J. Org. Chem. 2014, 10, 1589–1595, doi:10.3762/bjoc.10.164

• duplex due to having non-complementary DNA parts, and migrate on the gel like single strands 1, 6, and 7. These results underline the importance of the complementary DNA segments in aligning the pyrene and PDI chromophores for optimal interaction. Conclusion A series of DNA oligonucleotides

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

• synthetic oligonucleotides (Thermo-Fisher Scientific, HPLC-grade) were prepared in double-distilled water, and the PNA concentration was calculated by UV absorbance with the following extinction coefficients (ε260 [M–1cm–1]) for the nucleobases: T 8600, T* 14938 (pyrene-modified monomer, see Supporting

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

• nucleobases can be performed simultaneously by treatment with aqueous ammonia as in the solid phase synthesis of native oligonucleotides (ODN) [21]. The oxalyl-mediated attachment of the growing chain to the solid support is usual in the synthesis of base sensitive ODN derivatives [22]. Figure 3 indicates the

• previously used in the synthesis of PMO in the 2→4 direction [23]. This corresponds to the 5’→3’ direction of native oligonucleotides. In our case, the MorGly oligomers were synthesized in the opposite direction (4→2) [20] similar to the standard direction (3’→5’) of native ODN and peptide nucleic acid (PNA

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

• 1,3,5-triethynylbenzene scaffold. The oligonucleotides should be directly fused to the benzene ring via the three acetylene modifications resulting in a Y-shape topology. Thereby a rigid core with reduced degrees of rotation will be generated in contrast to other approaches that used more flexible

• 4 [42] yielding 5 in acceptable yields (Scheme 1). Finally, compound 5 was transformed into 6 by phosphitylation resulting in a building block that bears protection groups and reactive groups that are standard in solid phase DNA oligonucleotide synthesis. Synthesis of branched oligonucleotides. DNA

• respective DNA oligomers. Since we later intended to investigate whether the oligonucleotide branches are used as primers in PCR (vide infra), the oligonucleotides have to terminate with a free 3'-hydroxy group. This requires a particular synthesis strategy (Scheme 2). The synthesis strategy was adapted in a

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

• synthesis are the choice of the strategy (SPSS or LPS) and the method of nucleotide condensation. As mentioned in review [22], LPS is the preferable strategy for obtaining semi-preparative and preparative quantities of short oligonucleotides. This strategy was successfully used in the synthesis of native

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

• % CO2. Reporter gene assays The 1092 bp human survivin promoter (region between nucleotide 1821 and nucleotide 2912 within the human survivin gene; GenBankTM accession number U75285) was amplified by polymerase chain reaction from genomic DNA isolated from MonoMac6 cells using oligonucleotides derived

Synthesis of homo- and heteromultivalent carbohydrate-functionalized oligo(amidoamines) using novel glyco-building blocks

• Felix Wojcik,
• Sinaida Lel,
• Alexander G. O’Brien,
• Peter H. Seeberger and
• Laura Hartmann

Beilstein J. Org. Chem. 2013, 9, 2395–2403, doi:10.3762/bjoc.9.276

• oligonucleotides [14]. Such constructs have contributed to our current understanding of multivalent interactions [5]. Nevertheless, binding studies on multivalent compounds with different scaffold architectures or combinations of different sugar ligands are limited due to the often undefined chemical composition

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

• -43 and thus affect its cellular accumulation. In this study, several 4-aminoquinoline derivatives (Figure 8) were found to bind to TDP-43, decrease its association with oligonucleotides, and increase caspase-mediated cleavage of the protein [43]. Furthermore, treatment of H4 cells with these

Efficient Cu-catalyzed base-free C–S coupling under conventional and microwave heating. A simple access to S-heterocycles and sulfides

• Silvia M. Soria-Castro and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2013, 9, 467–475, doi:10.3762/bjoc.9.50

• synthesis of phosphorothioate oligonucleotides [57], was synthesized by the reaction of 2-mercaptobenzoic acid (7) with KSCOMe (1), probably through the intermediate 8 (Scheme 3) [58]. We envisioned that compound 6 could be easily achieved by a cascade process starting with the copper-mediated reaction of 2

Glycosylation efficiencies on different solid supports using a hydrogenolysis-labile linker

• Mayeul Collot,
• Steffen Eller,
• Markus Weishaupt and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 97–105, doi:10.3762/bjoc.9.13

• introduced the concept of solid-phase peptide synthesis in 1963 [1], synthesis on solid supports has evolved as a powerful tool for organic chemists [2]. Over the past fifty years this strategy has been successfully applied to the synthesis of other biopolymers, such as oligonucleotides [3] and

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

• oligonucleotides [5][6][7][11][12][13] displaying only very little toxicity towards mammalian cells [11]. They have also been shown to function in the recognition of biomacromolecules. Likewise, other polycationic species, such as the N-alkylated glycine oligomers (peptoids) [14][15][16][17][18][19][20][21][22][23

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

• Honeycutt et al. [14] used palmitic acid to deliver a protease inhibitor into cells, and Bradley et al. [15] used docosahexanoic acid to improve the uptake of paclitaxel into tumor cells. For a review see Wong and Toth [16]. Of particular interest was the incorporation of anti-sense oligonucleotides into

• ] reported the internalization by polylysine of methothrexate and horse radish peroxidase; Leonetti et al. [21] the internalization of oligonucleotides; and Mulders et al. [22] the internalization of adenovirus into cells. A polylysine peptoid derivative was used by Murphy et al. [23] for “gene delivery

Dimerization of a cell-penetrating peptide leads to enhanced cellular uptake and drug delivery

• Jan Hoyer,
• Ulrich Schatzschneider,
• Michaela Schulz-Siegmund and
• Ines Neundorf

Beilstein J. Org. Chem. 2012, 8, 1788–1797, doi:10.3762/bjoc.8.204

• variety of cargo molecules for therapy and diagnosis, as could be successfully shown for, e.g., cytostatics [1], proteins [2], oligonucleotides [3][4] and nanoparticles [5]. A common feature of CPPs is their typically high content in basic arginine and lysine residues, leading to a positive net charge of

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

• photochromic nucleosides. All nucleosides were characterized with respect to their absorption and photochromic properties. Based on these results, the most promising photochromic DNA base modification was incorporated into representative oligonucleotides by using automated phosphoramidite chemistry. The

• [29][30], into oligonucleotides (Scheme 1). Although the spiropyran DNA building blocks 1 and 2 exhibit promising photochromic properties as nucleosides, it is not worth pursuing this synthetic direction further for the following reasons [30]: (i) It is reported that spiropyrans decompose in aqueous

• representative oligonucleotides by using automated phosphoramidite chemistry, and characterized with respect to its photochromism in DNA. Results and Discussion Design and synthesis of diarylethene-modified 2’-deoxyuridines 4–6 The typical way to tether fluorophores to oligonucleotides is to use an alkyl chain

Syntheses and applications of furanyl-functionalised 2,2’:6’,2’’-terpyridines

• Jérôme Husson and
• Michael Knorr

Beilstein J. Org. Chem. 2012, 8, 379–389, doi:10.3762/bjoc.8.41

• . Finally, the hydrolysis of the ester moieties followed by complexation to Eu(III) yielded the lanthanide complex 65 (Scheme 12). This synthetic sequence was used to demonstrate the possibility to prepare labelled oligonucleotides starting from azido-functionalised ones and alkynyl-containing terpyridines

Synthesis, reactivity and biological activity of 5-alkoxymethyluracil analogues

• Lucie Brulikova and
• Jan Hlavac

Beilstein J. Org. Chem. 2011, 7, 678–698, doi:10.3762/bjoc.7.80

• and finally treated with methanolic ammonia to afford nucleosides 126 and 127. Synthesis of oligonucleotide intermediates Modified oligonucleotides are powerful tools in nucleic acid research and their synthesis has become an important aspect of bioorganic and medicinal chemistry. One part of

• oligonucleotides can also serve as a tool for the investigation of interactions between NF-κB proteins (NF-κB is a protein complex that controls the transcription of DNA and plays a key role in regulating the immune response to infection). A study was reported by Kittaka and co-workers [38] which described an

• interaction between the above noted proteins and modified oligonucleotides, in which thymidine is replaced by a 5-formyl derivative. A phosphoramidite 145 for oligonucleotide synthesis was prepared from O2-2'-cyclouridine (135) by a multistep synthesis (Scheme 24). In a first step, O2-2'-cyclouridine (135

Functionalized polymers: synthesis and properties

• Helmut Ritter

Beilstein J. Org. Chem. 2010, 6, No. 55, doi:10.3762/bjoc.6.55

• chromatography), for membranes and in the solid phase synthesis of peptides and oligonucleotides. Focusing on the constantly developing medical field, only specifically elaborated functional polymer materials can fulfill the specific challenges required of them for use as, for example, surgical sutures, dental

(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

• units present, more so than is the case with other biomolecules such as polypeptides or oligonucleotides. This is determined by the stereochemical identity of the monosaccharide units present (e.g. glucose, galactose, mannose), their glycosidic linkage positions (e.g. 1→4, 1→6), the nature at anomeric

• hexamer adopted a repeating β-turn structure [51] dictated by internal 10-membered hydrogen bonded rings. Such conformations are similar to those reported for the δ-2,5-cis-oxetane-THF oligomers [37]. D’Onofrio et al. [52] have carried out solid phase synthesis of oligonucleotides conjugated at the 3

• ′ terminus with (1→6)-amide-linked oligosaccharide mimics (Figure 9). The presence of the saccharide unit at the 3′-end of 18-mers significantly enhanced the stability of the oligonucleotides in bovine fetal serum, non-negatively interfering with their ability to form stable duplexes with complementary DNA

Synthetic incorporation of Nile Blue into DNA using 2′-deoxyriboside substitutes: Representative comparison of (R)- and (S)-aminopropanediol as an acyclic linker

• Daniel Lachmann,
• Sina Berndl,
• Otto S. Wolfbeis and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2010, 6, No. 13, doi:10.3762/bjoc.6.13

• Nile Blue chromophore was incorporated into oligonucleotides using “click” chemistry for the postsynthetic modification of oligonucleotides. These were synthesized using DNA building block 3 bearing an alkyne group and reacted with the azide 4. (R)-3-amino-1,2-propanediol was applied as the linker

• ]. Bioorthogonality is required for these ligation reactions in that both the functional group of the oligonucleotides and the functional group of the modifier should not be present in typical biomolecules and should react selectively with each other [11]. Over the last five years the Huisgen–Meldal–Sharpless “click

• visible spectrum) for use in “click” conjugation have been reported meanwhile [18]. The dye carrying the azide group was reacted with an alkyne group that was incorporated into the oligonucleotides as a nucleotide substituent. (S)-3-Amino-1,2-propanediol was used as an acyclic linker and substitute for