Synthesis, biophysical properties, and RNase H activity of 6’-difluoro[4.3.0]bicyclo-DNA

• Sibylle Frei,
• Adam K. Katolik and
• Christian J. Leumann

Beilstein J. Org. Chem. 2019, 15, 79–88, doi:10.3762/bjoc.15.9

• 3’-adjacent nucleotide are thought to favourably contribute in both F-RNA and F-ANA duplexes [13]. Furthermore, in duplexes of the F-ANA with complementary RNA, internucleosidic C–H···F–C pseudohydrogen bonds are proposed at pyrimidine-purine steps to additionally stabilize the structure [14][15

• fluorine atom pointing into the minor groove. Conversely, in the Ara-FHNA, repulsive electrostatic interactions between the fluorine atom and the 4’-oxygen of the 3’-adjected nucleotide resulted in a partial unstacking of the nucleobases and a destabilizing effect upon duplex formation [26]. Also other

New standards for collecting and fitting steady state kinetic data

• Kenneth A. Johnson

Beilstein J. Org. Chem. 2019, 15, 16–29, doi:10.3762/bjoc.15.2

• complex in the open state with a primer strand n residues long, while FDnN represents the closed state with nucleotide (N) bound. Note that we show 1/K1 = 200 μM for the initial weak binding step. The initial weak binding of nucleotide to the open state (Kd = 200 μM) is followed by a very fast

• energy profile for correct nucleotide incorporation with that for a mismatch (Figure 7). With a mismatch (dashed line), the chemistry step becomes very slow, while the rate of enzyme opening is much faster. Thus, for a mismatch, the conformational change step comes to equilibrium prior to rate-limiting

Thermophilic phosphoribosyltransferases Thermus thermophilus HB27 in nucleotide synthesis

• Ilja V. Fateev,
• Ekaterina V. Sinitsina,
• Aiguzel U. Bikanasova,
• Maria A. Kostromina,
• Elena S. Tuzova,
• Larisa V. Esipova,
• Tatiana I. Muravyova,
• Alexei L. Kayushin,
• Irina D. Konstantinova and
• Roman S. Esipov

Beilstein J. Org. Chem. 2018, 14, 3098–3105, doi:10.3762/bjoc.14.289

• , 117997, Russia 10.3762/bjoc.14.289 Abstract Phosphoribosyltransferases are the tools that allow the synthesis of nucleotide analogues using multi-enzymatic cascades. The recombinant adenine phosphoribosyltransferase (TthAPRT) and hypoxanthine phosphoribosyltransferase (TthHPRT) from Thermus thermophilus

• phosphoribosyltransferase; catalysis; enzyme; hypoxanthine phosphoribosyltransferase; multi-enzyme cascade; nucleotides; thermophiles; Introduction Bacterial phosphoribosyltransferases are used in multi-enzymatic cascades that perform nucleotide synthesis de novo [1][2]. Recently, we reported on the possibility of cascade

• APRT limits the number of possible nucleotides that can be synthesized. Thus, for Thermus thermophilus HB27 APRT (TthAPRT), nucleotide synthesis is limited to the closest structural homologs of adenine (Table 1) [1]. Unfortunately, 1,2,4-triazole-3-carboxamide, its analogues, guanine, hypoxanthine, and

6’-Fluoro[4.3.0]bicyclo nucleic acid: synthesis, biophysical properties and molecular dynamics simulations

• Sibylle Frei,
• Andrei Istrate and
• Christian J. Leumann

Beilstein J. Org. Chem. 2018, 14, 3088–3097, doi:10.3762/bjoc.14.288

• polarizability of the modified nucleotide, and therefore influences the metabolic stability, the membrane permeability, the RNA- and protein-binding affinity of the AON [25][26][27][28][29]. Over the last almost two decades, fluorinated oligonucleotide analogs like 2’-deoxy-2’-fluoro-RNA (F-RNA) [26][30][31], 2

Learning from B₁₂ enzymes: biomimetic and bioinspired catalysts for eco-friendly organic synthesis

• Keishiro Tahara,
• Ling Pan,
• Toshikazu Ono and
• Yoshio Hisaeda

Beilstein J. Org. Chem. 2018, 14, 2553–2567, doi:10.3762/bjoc.14.232

• use of vitamin B12 [116]. Furthermore, cobalester, an amphiphilic vitamin B12 derivative with six ester groups and a nucleotide loop, has recently been developed to show good catalytic activity for C–C bond forming reactions [117][118]. The above-mentioned visible-light-driven system composed of 1

Semi-synthesis and insecticidal activity of spinetoram J and its D-forosamine replacement analogues

• Kai Zhang,
• Jiarong Li,
• Honglin Liu,
• Haiyou Wang and
• Lamusi A

Beilstein J. Org. Chem. 2018, 14, 2321–2330, doi:10.3762/bjoc.14.207

• of spinosyns via chemical modification [18]. Bioactivities of many microbial secondary metabolites are highly dependent on their sugar constituents which are transferred as nucleotide-activated sugars to an aglycon by glycosyltransferases [19]. Therefore, bioactivities of these metabolites could

Synthesis of new p-tert-butylcalix[4]arene-based polyammonium triazolyl amphiphiles and their binding with nucleoside phosphates

• Vladimir A. Burilov,
• Guzaliya A. Fatikhova,
• Mariya N. Dokuchaeva,
• Ramil I. Nugmanov,
• Diana A. Mironova,
• Pavel V. Dorovatovskii,
• Victor N. Khrustalev,
• Svetlana E. Solovieva and
• Igor S. Antipin

Beilstein J. Org. Chem. 2018, 14, 1980–1993, doi:10.3762/bjoc.14.173

• attention to the synthesis of host molecules with high affinity to biologically important anions [1][2][3][4][5]. Among these anions, nucleotide recognition and sensing represents an especially important research area due to the great biological significance of these anions. Adenine-containing nucleotides

• nucleotides must possess selectivity towards these anions. From this point of view, nucleotide receptors based on polyammonium cations are of great demand because the electrostatic interactions of such polyammonium systems and negatively charged phosphates are strong. Hydrogen bonding [8] and π-stacking

• interactions between the adenine groups of the nucleotide and the receptor’s aromatic moieties [9] can additionally contribute to the complex stability and binding selectivity. Polyammoniums mimic the biologically important acyclic polyamines such as putrescine, spermidine, and spermine, which have strong

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• exploited grinding to facilitate disaggregation of DNA from tightly bound proteins through selective denaturation of the latter. Despite the wide application of ball milling to amino acid chemistry, there have been limited reports of mechanochemical transformations involving nucleoside or nucleotide

• substrates on preparative scales. A survey of these reactions is provided, the majority of which have used a mixer ball mill and display an almost universal requirement for liquid to be present within the grinding vessel. Mechanochemistry of charged nucleotide substrates, in particular, provides considerable

• : specifically, solid solutions, cocrystals, polymorph transitions, carbon nanotube dissolution and inclusion complex formation. Keywords: DNA; green chemistry; mechanochemistry; nucleoside; nucleotide; Introduction Several definitions of mechanochemistry have been attempted since Ostwald included it as one of

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

• of nucleases by pH-rate dependency, X-ray crystallography, amino acid/nucleotide substitution and computational approaches, experimental and theoretical studies with small molecular model compounds still play a role. With small molecules, the importance of various elementary processes, such as proton

• protein nucleases and ribozymes a subject of intensive mechanistic studies. pH-Rate dependency, X-ray structures, amino acid/nucleotide substitution experiments and the effect of thiosubstitution of phosphate oxygens on the binding of metal ion cofactors have given invaluable information about the

• nucleotide are extensively used in mechanistic studies of protein nucleases and ribozymes. Rate accelerating 3´-bridging substitution has been used to find out whether the chemical step really is rate-liming and 5´-substitution to verify that some small ribozymes utilize general acid catalysis [40]. The

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• acids. Shown is the monomeric building block of nucleic acids. Changes to the nucleotide structure can affect molecular recognition, as well as structure and function. Formation of oxocarbenium ion during glycosidic bond cleavage in nucleosides [31]. The extent of leaving group stabilization and

An uracil-linked hydroxyflavone probe for the recognition of ATP

• Márton Bojtár,
• Péter Zoltán Janzsó-Berend,
• Dávid Mester,
• Dóra Hessz,
• Mihály Kállay,
• Miklós Kubinyi and
• István Bitter

Beilstein J. Org. Chem. 2018, 14, 747–755, doi:10.3762/bjoc.14.63

• this probe to include complementary base-pairing interactions. The theoretical calculations revealed the availability of multiple complex structures. The synthesis was performed using click chemistry and the nucleotide recognition properties of the probe were evaluated using fluorescence spectroscopy

• ; nucleotide recognition; Introduction Nucleotides play essential roles in various physiological processes, such as energy transportation [1], DNA synthesis [2] and cell signaling events [3]. Especially, adenosine-5’-triphosphate (ATP) is vital, since it is the main energy source in living systems [4]. The

• additional recognition sites to existing nucleotide receptor molecules can lead to multi-point recognition and enhanced selectivity/sensitivity for ATP chemosensors. In our ongoing research, we are interested in the exploration of the function of complementary base-pairing in ATP recognition as a possible

Enzyme-free genetic copying of DNA and RNA sequences

• Marilyne Sosson and
• Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

• . Instead, the base pairing between individual bases of an incoming nucleotide and the templating base must suffice to attract the monomer to the extension site. The stability of different base pairs varies, and so does the templating effect of different stretches of the template sequence. Using random

• extension. The hydrolyzed, free nucleotide can still bind to the extension site on the template, and in doing so, prevent the activated form from entering the site, acting as a competitive inhibitor [32]. So, both the rate of hydrolysis and the strength of the inhibitory effect were important factors to be

• considered in a quantitative model. Figure 7 shows our model for an RNA-based primer extension system. For primer extension to occur, binding between activated nucleotide and primer–template duplex takes place. So, the dissociation constant (Kd) has to be determined experimentally [33]. Once bound, the

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• the modification in the nucleotide: the internucleosidic phosphate, the nucleobase, the sugar or the extremities of ONs. Moreover, the review provides a current and detailed account of stimuli-responsive ONs with the main goal of gene silencing. However, for some stimuli-responsive ONs reported in

• conjugate with a disulfide linker is favorable to improve the suppression of 2’,3’-cyclic nucleotide 3’-phosphodiesterase mRNA in oligodendrocytes in vivo. This result may be attributable to increased bioavailability of siRNA in the cytoplasm. Similarly, regarding the intracellular delivery of naked peptide

• phosphate modifications cleaved under carboxyesterase mediation was envisaged for ONs more than 20 years ago and was extensively studied by Imbach’s group [29] and others [22][30][31]. Ten years ago, Lönnberg summarized the chemical aspects of prodrug strategies at the nucleotide and oligonucleotide levels

Preparation of trinucleotide phosphoramidites as synthons for the synthesis of gene libraries

• Ruth Suchsland,
• Bettina Appel and
• Sabine Müller

Beilstein J. Org. Chem. 2018, 14, 397–406, doi:10.3762/bjoc.14.28

• partially circumvent this problem, like using NNS instead of NNN codons (with N = A, C, G, T; S = C, G) taking advantage of redundancy of the third nucleotide positions in the majority of codons [10], or using spiked oligonucleotides [11], which are synthesized from solutions of the four nucleotide building

• blocks, each of those contaminated with a "spiking mix" consisting of equal aliquots of each of the four building blocks [9][12]. The required volume of the spiking mix to achieve a desired amount of nucleotide replacements at a defined position of the oligonucleotide can be calculated, such that library

• synthons for codon-based synthesis of a desired primer [18]. Taking the example from above, for a DNA fragment encoding three randomized amino acids, instead of nine nucleotide positions to be randomized, variation of trinucleotides (codons for the 20 amino acids) at only three positions is required

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

• nucleotide polymorphisms (SNP), insertions and deletions [74][75][76]. They have also been used for the detection and quantification of ribosomal RNA in a wash-free FISH [77]. Side-by-side comparison showed that the PNA beacons gave faster hybridization kinetics, a higher signal-to-noise ratio and a much

Polarization spectroscopy methods in the determination of interactions of small molecules with nucleic acids – tutorial

• Tamara Šmidlehner,
• Ivo Piantanida and
• Gennaro Pescitelli

Beilstein J. Org. Chem. 2018, 14, 84–105, doi:10.3762/bjoc.14.5

• adequately prepared and characterized. For that reason, a short description of the most important issues in sample preparation is summarized in chapters 2.2 and 2.3. 2.1. Relation between DNA or RNA secondary structure and polarization spectroscopy Nucleobases are achiral but nucleoside and nucleotide

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

Beilstein J. Org. Chem. 2017, 13, 2819–2832, doi:10.3762/bjoc.13.274

• first nucleotide (cap1), a modification which is commonly observed in eukaryotes [13][14][15]. Besides cap0 and cap1, cap structures with further modifications exist. Additional methyl groups are often found at the second nucleotide (cap2) while in trypanosomes up to four methylated nucleotides are

• achieved with the capping enzyme of the model organism Paramecium bursaria Chlorella virus-1 (PBCV-1) by Bisaillon and co-workers [45]. Out of 22 nucleotide analogues tested in this study, 13 were found to form a covalent complex with the PBCV-1 guanylyltransferase (GTase) while 11 were actually

• transferred onto a 5′-diphosphate RNA (Figure 2). Moreover, RNAs capped with those nucleotide analogues were translated even in the absence of the N7-methyl group when alternative modifications enabled binding to eIF4E [45]. Co-transcriptional capping In co-transcriptional capping, cap analogues are added

Metal-mediated base pairs in parallel-stranded DNA

• Jens Müller

Beilstein J. Org. Chem. 2017, 13, 2671–2681, doi:10.3762/bjoc.13.265

• parallel-stranded one is the formal dissociation of one of its component strands into nucleotides, the rotation of each nucleotide by 180° along the long axis of the base pair, and reconnection of the backbone of that strand. This essentially reverts the Watson–Crick base pairs to give reversed Watson

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• inhibitor of the human farnesyl pyrophosphate synthase (hFPPS) [181] were prepared from their corresponding diethylphosphonates (Figure 18). Nucleotide analogues were also prepared by this methodology as exemplified by the compound 54 [176] or 55 [182]. For these last two examples, the bromotrimethylsilane

Enzymatic synthesis of glycosides: from natural O- and N-glycosides to rare C- and S-glycosides

• Jihen Ati,
• Pierre Lafite and
• Richard Daniellou

Beilstein J. Org. Chem. 2017, 13, 1857–1865, doi:10.3762/bjoc.13.180

• donor (lipid, nucleotide…) [13]. It is considered that GTs are encoded by 1% of total genes, and over 300 000 representatives of GT superfamily have been classified according to their nucleotide sequence into 103 subfamilies [8]. Depending on the conservation of the anomeric atom stereochemistry of the

Effect of uridine protecting groups on the diastereoselectivity of uridine-derived aldehyde 5’-alkynylation

• Raja Ben Othman,
• Mickaël J. Fer,
• Laurent Le Corre,
• Sandrine Calvet-Vitale and
• Christine Gravier-Pelletier

Beilstein J. Org. Chem. 2017, 13, 1533–1541, doi:10.3762/bjoc.13.153

• ; nucleoside; protecting groups; uridine; Introduction Nucleoside and nucleotide derivatives or analogues are biologically active compounds of major interest [1][2]. Their widespread applications span from therapeutic agents, such as antibacterial [3][4][5], antiviral [6] or antitumor [7][8] drugs, to

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• the complete absence of protecting groups in an aqueous environment using 2-chloro-1,3-dimethylimidazolinium chloride (DMC) and a mild amine base (NEt3) (see chapter 4.1). 2.1.2 Glycosyltransferases: Glycosyltransferases (GTs) catalyze the transfer of a carbohydrate from an activated nucleotide

Towards open-ended evolution in self-replicating molecular systems

• Herman Duim and
• Sijbren Otto

Beilstein J. Org. Chem. 2017, 13, 1189–1203, doi:10.3762/bjoc.13.118

• autocatalytic cycles to more complex systems was observed. Such cooperative systems are capable of complexification and natural selection and can therefore be of importance in bridging the gap between replication of simple short RNA molecules from nucleotide building blocks and the formation of more complex

From chemical metabolism to life: the origin of the genetic coding process

• Antoine Danchin

Beilstein J. Org. Chem. 2017, 13, 1119–1135, doi:10.3762/bjoc.13.111

• picture of the corresponding molecules. Remarkably, the link between the genetic program and the effectors of biological processes of the machine that runs the program, the proteins, is mediated by such a code, the genetic code, which establishes a correspondence between the nucleotide building blocks

• aromatic heterocycles) is based on the incorporation of amino acids in the core of nucleotide precursors. Pyrimidine nucleotide biosynthesis uses aspartate and combines together ubiquitous molecules, water, carbon dioxide, ammonium and phosphate (forming carbamoyl phosphate, also a precursor of arginine

• the 3D grooves of the double helix were of 20 different types, exactly matching the number of proteinogenic amino acids. Each pocket is defined by specific arrangements of the four nucleotide bases. This “diamond code” is made of 20 overlapping triplets suggesting that each amino acid in the

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261

• neglected. Similar conclusions were made by Paal and Szeijtli [103]. iv) Complexation of nucleic acids Nucleic acids are macromolecules, where the monomer is the nucleotide. Each nucleotide has three components: a 5-carbon sugar, a phosphate group, and a nitrogenous base. These nucleotides are joined by