Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• polynucleotides. Among several examples, the most intriguing pH controlled binding of nucleotides and nucleic acids showed bis-phenanthridine triamine [59] (8, Scheme 22). Compound 8 intercalated with only one phenanthridinium subunit into all ds-DNA and ds-RNA, while additional interactions of the other subunit

• respect to other nucleotides. In addition, the observed selectivity towards poly(G) and poly(A) can be beneficial in biological applications for instance to influence the mRNA-function via binding to the poly(A) tail [62][63][64] and inhibition of the HIV-1 replication by targeting recognition of the

• phenanthridine ring (Scheme 23). The phenanthridinium–nucleobase conjugates did not show targeted selectivity toward complementary nucleotides in aqueous medium due to the strong competition of bulk water with the expected hydrogen bonds [70][71]. Fortuitously, the hydrophobic environment within the common DNA

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

• fragments of synthetic single-stranded DNA. This strategy uses an artificially expanded genetic information system (AEGIS) that adds nucleotides to the four (G, A, C, and T) found in standard DNA by shuffling hydrogen-bonding units on the nucleobases, all while retaining the overall Watson–Crick base

• study that attempted to assemble similarly sized genes with optimally designed standard nucleotides lacking AEGIS components gave successful assemblies of up to 16 fragments, but generally failed when larger autonomous assemblies were attempted. Conclusion: AEGIS nucleotides, by increasing the

• vision, now called “synthetic biology” [13][14][15][16][17], of converting automatically synthesized short DNA molecules (50–100 nucleotides in length) into much longer DNA constructs by autonomous self-assembly, without the cost of manual convergent assembly. In addition to the DARPA Foundries “1,000

Specific DNA duplex formation at an artificial lipid bilayer: fluorescence microscopy after Sybr Green I staining

• Emma Werz and
• Helmut Rosemeyer

Beilstein J. Org. Chem. 2014, 10, 2307–2321, doi:10.3762/bjoc.10.240

• the intercalating dye. The results described above offer several possibilities of interpretation: The target strand 9 carries 3’-terminally to the recognition site of the lipo-oligonucleotide 4 an overhang of 6 nucleotides in length. Therefore, duplex formation between 4 and 9 over a full length of 12

• they do neither form hair pins nor self-complementary duplexes. The lipophilized strand and the complementary oligomer contain the same number of all canonical nucleotides, so that a mixture of 1 A260 units, each of both strands gives an equimolar mixture. For nearly all base pairs nearly all nearest

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

• nucleotides mimicking these alkylation products have been synthesized and then converted into the phosphoamidite building block for chemical DNA synthesis [6][7][18][19][20][21][22][23][24][25][26][27][28]. Not only do these protocols require extensive chemical synthesis, but the sequence of the synthesized

• duplex ODN cannot be freely chosen since after incorporation of the linked dinucleotide both DNA strands are elongated in parallel and therefore are identical in sequence. If the linked base pair is not incorporated at the 5’ end but in the middle of a duplex, the nucleotides 3' to the linkage in the 2nd

• additional linker atoms avoiding the risk of steric interference with protein binding [42][43][44][45][46]. A disulfide cross-link between 2'-deoxy-6-thioguanosine (dG6S) and dU4S was used to study the specificity of the human flap endonuclease FEN1 and confirmed that unpairing the two terminal nucleotides

Solution phase synthesis of short oligoribonucleotides on a precipitative tetrapodal support

• Alejandro Gimenez Molina,
• Amit M. Jabgunde,
• Pasi Virta and
• Harri Lönnberg

Beilstein J. Org. Chem. 2014, 10, 2279–2285, doi:10.3762/bjoc.10.237

• support-bound oligonucleotides precipitated quantitatively from MeOH, while the unreacted building block and small molecular reagents remained in the filtrate (Figure 1). No sign of the HPLC signal referring to the support bound nucleotides (tR = 20.14 min) could be detected in the liquid phase. In

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

• 2’-propargylated nucleotides and azide-modified Nile red [19]. An approach related to the latter was used in this work, although the azide function was placed on the PNA instead of the Nile red, and the clicking was carried out on the solid support rather than in solution phase. The propargylated

Photorelease of phosphates: Mild methods for protecting phosphate derivatives

• Sanjeewa N. Senadheera,
• Abraham L. Yousef and
• Richard S. Givens

Beilstein J. Org. Chem. 2014, 10, 2038–2054, doi:10.3762/bjoc.10.212

• substrate. This limits the useful absorption range to ca. 350 to 400 nm for heterolysis by a primary photochemical pathway. Phosphates hold a central historic position in caged photochemistry through their cross-disciplinary significance in both biology and chemistry. Nucleotides (especially ATP, cAMP, and

• is reliable when extended to more complex phosphate leaving groups including nucleotides such as ATP and GTP and tyrosyl phosphates and thiophosphates [52][53][54][55]. The key comparisons for practical applications of photochemical deprotection are the maximum conversion which controls the chemical

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

• of a conformational analysis show that the alkylation/acylation can be effectively used for tuning the pyrrolidine conformation over the whole pseudorotation cycle. Keywords: conformation; NMR; nucleic acids; nucleotide analog; phosphonic acid; pseudorotation; pyrrolidine; Introduction Nucleotides

• , nucleosides and nucleobases play an important role in all biological systems. Therefore, it is not surprising that many of their analogs possess interesting biological properties. Potent antiviral drugs based on phosphonate nucleotides 1a–c [1][2], 2a–d and 3a–d (Figure 1) have been reported. Prodrugs of

• acyclic compounds 1a–c are currently in clinical use for the treatment of diseases caused by DNA viruses and retroviruses. Cyclic analogs 2 and 3 were reported to exhibit antiviral activity against HIV strains [3]. These examples show that the modification of the sugar-phosphate moiety in nucleotides is a

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

• RNA catalysts that support an aldol reaction between an aldehyde and a ketone, relevant to the synthesis of sugars [6], or the linkage of ribose to nucleobases to generate nucleotides [7]. Such ribozymes are seen as important functional entities underscoring the RNA world theory, where ribonucleic

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

• arrangement of γ and a somewhat attenuated but clear preference for an S-type furanose conformation. Oligonucleotide synthesis The dodecamers ON1–4, shown in Table 2, containing one to two modifications, were synthesized in order to test the consequences of the two modified bicyclic nucleotides on RNA and DNA

• oligonucleotides under the conditions of measurement. The corresponding Tm-data are summarized in Table 2. The bcen-T modification destabilizes duplexes with complementary DNA by −1.4 to −2.0 °C per modification relative to dT in a somewhat sequence dependent context. If flanked by two pyrimidine nucleotides (ON1

• ) DMTrCl, pyridine, rt, 16 h, 29% of 12α and 34% of 12β (over two steps); (c) CEP-Cl, DIPEA, THF, rt, 1 h, 94%. Pathways for elimination of the modified nucleotides during the oxidation step in oligonucleotide assembly. Selected backbone torsion angles and sugar pucker data for 8β and 11β and related bi

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

• 17, Alachua, FL 32615, USA 10.3762/bjoc.10.192 Abstract Synthetic biologists wishing to self-assemble large DNA (L-DNA) constructs from small DNA fragments made by automated synthesis need fragments that hybridize predictably. Such predictability is difficult to obtain with nucleotides built from

• just the four standard nucleotides. Natural DNA's peculiar combination of strong and weak G:C and A:T pairs, the context-dependence of the strengths of those pairs, unimolecular strand folding that competes with desired interstrand hybridization, and non-Watson–Crick interactions available to standard

• DNA, all contribute to this unpredictability. In principle, adding extra nucleotides to the genetic alphabet can improve the predictability and reliability of autonomous DNA self-assembly, simply by increasing the information density of oligonucleotide sequences. These extra nucleotides are now

A promising cellulose-based polyzwitterion with pH-sensitive charges

• Thomas Elschner and
• Thomas Heinze

Beilstein J. Org. Chem. 2014, 10, 1549–1556, doi:10.3762/bjoc.10.159

• example proteins, nucleotides, and polysaccharides like alginates. Synthetic ionic polymers are widely used in the field of water treatment [2], protein separation, desalination, binding of metal ions, in the oil industry [3] and nanotechnology [4]. In general, these polymers may be divided into water

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

• transport (a major reservoir for HIV) [29] and some alkyl and alkyloxyalkyl esters of nucleotides or acyclic nucleoside phosphonates have been explored in clinical studies [30]. In order to obtain the ester derivatives, 11-(acetylthio)undecanoic acid, obtained from 11-bromoundecanoic acid and potassium

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

• ][35]. Furthermore, it has been shown that branched DNA constructs can form materials by self-assembly [36]. Richert et al. were able to generate DNA based materials based on branched DNA molecules which are non-covalently bound to each other by only hybridization of 2 nucleotides [37]. Interestingly

• different shapes which are further characterized in solution by DLS. EPR measurements further corroborate network formation and suggest rather rigid DNA networks. As demonstrated, the approach allows to additionally modify the networks by using chemically modified nucleotides during PCR. The depicted

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

• photoinitiating agents for electron transfer from nucleotides and amino acids [15][16][17][18]. Based on the above mentioned reasons, we have chosen 4-benzoylbenzoic acid, 2’-deoxyguanosine, and L-tryptophan [7][9][13][14][15][16][17][18][19][20] as the dye, nucleoside, and amino acid building blocks

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

• preparation of substituted pyridines. Many antiviral agents show a close structural resemblance to the nucleotides uracil, thymine and cytosine. Lamivudine (3.1) or zidovudine (3.2) are typical examples of pyrimidines/pyrimidones bound to a ribose-analogue (Figure 9) [83]. These molecules function by

Methylidynetrisphosphonates: Promising C₁ building block for the design of phosphate mimetics

• Vadim D. Romanenko and
• Valery P. Kukhar

Beilstein J. Org. Chem. 2013, 9, 991–1001, doi:10.3762/bjoc.9.114

• and coordination properties thus providing excellent possibilities for the design of effective phosphate mimetics. Especially successful so far seem to be approaches for the synthesis of trisphosphonate-modified nucleotides and nucleosides, which represent a promising class of potential drugs [8

• acid via trisphosphonate salt 38. Synthesis of halomethylidynetrisphosphonate salts 43 and 44 by modified Gross’s procedure. Synthesis of trisphosphonate modified nucleotides. Reagents: i, 5'-O-tosyl adenosine, MeCN; ii, AMP–morpholidate (0.8 equiv), tetrazole, pyridine; iii, AMP–morpholidate (5 equiv

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

• binding of TDP-43 to nucleotides. Cassel et al. [42] developed a high-throughput screening assay whereby TDP-43 nucleotide binding could be assessed. A screen of 7360 compounds yielded a series of small molecules that disrupt oligonucleotide binding to TDP-43 protein [42]. Later, this series of 4

A chemist and biologist talk to each other about caged neurotransmitters

• Graham C.R. Ellis-Davies

Beilstein J. Org. Chem. 2013, 9, 64–73, doi:10.3762/bjoc.9.8

• active molecules to be synthesized with photochemically protecting groups at their active sites were nucleotides [1][2]. Two reports appeared in 1977 and 1978 describing the synthesis of ortho-nitrobenzyl derivatives of cyclic-AMP [1] and ATP [2]. The photolabile cAMP derivative was one member of a

Studies on the substrate specificity of a GDP-mannose pyrophosphorylase from Salmonella enterica

• Lu Zou,
• Ruixiang Blake Zheng and
• Todd L. Lowary

Beilstein J. Org. Chem. 2012, 8, 1219–1226, doi:10.3762/bjoc.8.136

• sugar nucleotides is therefore a topic of continuing interest [6]. The classical method for chemically synthesizing sugar nucleotides involves the preparation of a sugar 1-phosphate derivative followed by its coupling to an activated nucleoside monophosphate to form the key pyrophosphate moiety (Figure

•  1A) [7]. In general, the yield of this process is low, and the purification of the product can be tedious; hence, the development of new methods to prepare sugar nucleotides remains an area of active research [6]. Although improved chemical methods have been developed [8][9][10][11][12][13], another

• attractive strategy is to employ a chemoenzymatic approach, in which a synthetic sugar 1-phosphate derivative is converted to the sugar nucleotide by a pyrophosphorylase (Figure 1B) [14][15]. This approach is increasingly used for the synthesis of sugar nucleotides, but a limitation is that the specificity

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

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

Mutational analysis of a phenazine biosynthetic gene cluster in Streptomyces anulatus 9663

• Orwah Saleh,
• Katrin Flinspach,
• Lucia Westrich,
• Andreas Kulik,
• Bertolt Gust,
• Hans-Peter Fiedler and
• Lutz Heide

Beilstein J. Org. Chem. 2012, 8, 501–513, doi:10.3762/bjoc.8.57

• ]; PemK binds to the promoter region of the Pem operon in E. coli. Finally, orf4 (2613 bp) showed homology to aminopeptidases. λ-RED recombination was used to delete the entire coding sequence of orf1 and the first 437 nucleotides of orf2 from the insert of cosmid ppzOS04 (Figure 1). After recombination

Dependency of the regio- and stereoselectivity of intramolecular, ring-closing glycosylations upon the ring size

• Patrick Claude,
• Christian Lehmann and
• Thomas Ziegler

Beilstein J. Org. Chem. 2011, 7, 1609–1619, doi:10.3762/bjoc.7.189

• therein). A remarkable differentiation of the regioselectivity of acylation reactions at differently exposed hydroxy groups was found for chiral 2’-O-tetrahydropyranyl nucleotides [51], whereby a particular hydroxy group is significantly deshielded in 1H NMR and consequently its nucleophilicity is thought