DNA functionalization by dynamic chemistry

• Zeynep Kanlidere,
• Oleg Jochim,
• Marta Cal and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2016, 12, 2136–2144, doi:10.3762/bjoc.12.203

• functional groups into its native structure [10][11]. Such chemically modified oligonucleotides are useful intermediates for their subsequent functionalization through post-synthetic protocols [11][12][13]. Within a post-synthetic strategy, a nucleotide analog is modified with a reactive functional group

Dinuclear thiazolylidene copper complex as highly active catalyst for azid–alkyne cycloadditions

• Anne L. Schöffler,
• Ata Makarem,
• Frank Rominger and
• Bernd F. Straub

Beilstein J. Org. Chem. 2016, 12, 1566–1572, doi:10.3762/bjoc.12.151

• ][22][23][24][25][26], nucleoside, nucleotide, and oligonucleotide chemistry [27][28][29], in fluorogenic reactions [30], and in the syntheses of dendrimers [25][31]. The detailed mechanism of this reaction and the exact role of copper(I) and the species involved in the catalytic cycle had remained

Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

• Tai Nguyen Van,
• Audrey Hospital,
• Corinne Lionne,
• Lars P. Jordheim,
• Charles Dumontet,
• Christian Périgaud,
• Laurent Chaloin and
• Suzanne Peyrottes

Beilstein J. Org. Chem. 2016, 12, 1476–1486, doi:10.3762/bjoc.12.144

• (cN-II), an enzyme involved in the regulation of purine nucleotide pools. NMR and molecular modelling studies showed that a few derivatives adopted similar structural features to IMP or GMP. Five derivatives were identified as modest inhibitors with 53 to 64% of cN-II inhibition at 1 mM. Keywords

• : cancer; cN-II inhibitors; nucleotide; phosphonate; triazole; Introduction Nucleotidases are an important family of enzymes involved in the metabolism of nucleotides [1]. In particular, human cytosolic 5’-nucleotidase II (cN-II) catalyses the dephosphorylation of purine 5’-monophosphate derivatives to

• sugar, and finally with Met53 and Lys292 for the phosphonate group, within the IMP-nucleotide binding site of cN-II. Experimental General procedure A for click reaction: The azido-sugar 2 (1 equiv) was dissolved in dry THF (45 mL/mmol) and the required alkyne derivative (5.4 equiv

Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

• Svetlana V. Vasilyeva,
• Vyacheslav V. Filichev and
• Alexandre S. Boutorine

Beilstein J. Org. Chem. 2016, 12, 1348–1360, doi:10.3762/bjoc.12.128

• interaction or the non-optimal structure of linkers that connect two components. Additional studies aiming to optimize the structure of the linker using molecular modeling are necessary. A) Formation of nucleotide triplets in parallel and antiparallel (relatively to polypurine strand) complexes. The relative

Effective in silico prediction of new oxazolidinone antibiotics: force field simulations of the antibiotic–ribosome complex supervised by experiment and electronic structure methods

• Jörg Grunenberg and
• Giuseppe Licari

Beilstein J. Org. Chem. 2016, 12, 415–428, doi:10.3762/bjoc.12.45

• the bacterial ribosome accumulated. In general, both ribosomal subunits can be targets of several natural or synthetic products, and in most cases, the specific binding sites are within the 16S-rRNA (30S subunit) or 23S-rRNA (50S subunit) nucleotide chains. The nucleotide skeleton of the ribosome

• pocket for the oxazolidinone ring is characterized by universally conserved 23S-rRNA nucleotides, leading to very similar ligand-bound conformations in different bacterial ribosomes [23]. From a theoretical point of view, the simulation of recognition processes employing nucleotide-based receptors is

• a pronounced flexibility. It might therefore be misleading to focus on the solid state structures of available nucleotide/guest complexes alone [25]. A third obstacle is the intrinsic deficiency of empirical force fields especially for DNA/RNA structures (“force-field polymorphism”). A thorough

Syntheses of 2-substituted 1-amino-4-bromoanthraquinones (bromaminic acid analogues) – precursors for dyes and drugs

• Enas M. Malik,
• Younis Baqi and
• Christa E. Müller

Beilstein J. Org. Chem. 2015, 11, 2326–2333, doi:10.3762/bjoc.11.253

• proposed the compound to interact with ATP-binding sites [33], and it was subsequently used as a pharmacological tool for studying ATP and other nucleotide receptors. RB-2 has played a crucial role in identifying different purine receptor subtypes, since it was found to selectively block only certain

• members of the nucleotide-activated purine P2 receptor family [34][35][36][37][38][39][40]. However, it should be mentioned that ever since the commercially available dye has been used as a tool compound in P2 receptor research, there has been some doubt about its identity and purity, both of which are

• potential as drug targets. In this context, a library of AQ derivatives, structurally related to RB-2, has been synthesized and evaluated at a variety of purinergic targets; all of which are characterized by a nucleotide binding site [28][42][43][44][45][46][47][48]. The nature of the substituent at

Engineering Pichia pastoris for improved NADH regeneration: A novel chassis strain for whole-cell catalysis

• Martina Geier,
• Christoph Brandner,
• Gernot A. Strohmeier,
• Mélanie Hall,
• Franz S. Hartner and
• Anton Glieder

Beilstein J. Org. Chem. 2015, 11, 1741–1748, doi:10.3762/bjoc.11.190

• and stop codons of the corresponding DAS gene was deleted as schematically depicted in Figure 2. In the case of Δdas1 Δdas2, the coding sequences of both genes were deleted in one step, thereby also removing HOB3, coding for a hypothetical guanosine nucleotide exchange factor. Characterization of

• in opposite direction. The two genes are separated by a short sequence encoding a hypothetical guanosine nucleotide exchange factor (HOB3). The target sites for the respective das knock-out cassettes are indicated schematically. Relative expression levels of the green fluorescent protein (GFP) in the

Towards inhibitors of glycosyltransferases: A novel approach to the synthesis of 3-acetamido-3-deoxy-D-psicofuranose derivatives

• Maroš Bella,
• Miroslav Koóš and
• Chun-Hung Lin

Beilstein J. Org. Chem. 2015, 11, 1547–1552, doi:10.3762/bjoc.11.170

• unknown [7]. In general, GTs transfer sugar nucleotide donors onto suitable acceptors during the biosynthesis of glycans and glycoconjugates [8]. Both donor and acceptor substrates are recognized by GTs binding pockets. For instance, in the course of biosynthesis of complex and hybrid oligosaccharides

• complexity of the GnTs catalytic mechanism. The main reasons originating from the complex character of the catalytic mechanism which complicate the search for GnTs inhibitors are a) participation of four components in the transition state (sugar donor, acceptor, nucleotide and metal co-factor), b) weak

Terminal lipophilization of a unique DNA dodecamer by various nucleolipid headgroups: Their incorporation into artificial lipid bilayers and hydrodynamic properties

• Emma Werz and
• Helmut Rosemeyer

Beilstein J. Org. Chem. 2015, 11, 913–929, doi:10.3762/bjoc.11.103

• shows the energy-minimized 3D structures of the lipophilic nucleoside headgroups 4a–9a. The reactive building blocks 4b–9b were subsequently used to synthesize the following lipo-oligonucleotides (LONs), which have an identical nucleotide sequence in common as well as a cyanine-5 (Cy5) fluorophore at

• in the total LONs, the hydration values amount to 0.8–1.2 g of H2O per gram of LON. Assuming, however, only hydration of the nucleic acid moiety, the hydration values amount to 0.5 g of H2O per g of molecules. From IR measurements it could be concluded that 20 water molecules hydrate one nucleotide

• residue within a nucleic acid [24][25]. This results in a hydration of 1 g of H2O per gram. However, Bloomfield et al. in 2000 [26] as well as Fernandes et al. in 2002 [23] reported hydration degrees of 0.35 [26] or 0.3 g of water per gram of nucleotide (Table 5). Confocal fluorescence lifetime analysis

Is organic chemistry science – and does this question make any sense at all?

• Andreas Kirschning and
• Thomas A. C. Reydon

Beilstein J. Org. Chem. 2015, 11, 893–896, doi:10.3762/bjoc.11.100

• conditions (molecular recognition, self-assembly and dynamic combinatorial chemistry) and how their molecular composition would be; the question why nature developed DNA and RNA that utilize ribose and 2-deoxyribose as central nucleotide building blocks instead of the more abundant and readily available

DNA display of glycoconjugates to emulate oligomeric interactions of glycans

• Alexandre Novoa and
• Nicolas Winssinger

Beilstein J. Org. Chem. 2015, 11, 707–719, doi:10.3762/bjoc.11.81

• the assembly of glycans in order to tailor spatial geometry [16]. Attractive features of this hybridization-based supramolecular scaffold are that double strand nucleic acid is fairly rigid with well-defined nucleotide spacing and that the valence and ligand combination can be adjusted through the

• -diazobenzoyl conjugates 1 and 2 with a guanidine nucleotide (G, derivatization at the 8-position) within DNA (Scheme 1) [18]. The conjugation was performed in solution on dsDNA and was used to introduce either lactose or cellobiose moieties (with and without linker). The substitution degree was proportional to

C-5’-Triazolyl-2’-oxa-3’-aza-4’a-carbanucleosides: Synthesis and biological evaluation

• Roberto Romeo,
• Caterina Carnovale,
• Salvatore V. Giofrè,
• Maria A. Chiacchio,
• Adriana Garozzo,
• Emanuele Amata,
• Giovanni Romeo and
• Ugo Chiacchio

Beilstein J. Org. Chem. 2015, 11, 328–334, doi:10.3762/bjoc.11.38

• structures in particular as antiviral or anticancer agents [1][2][3][4][5][6][7][8]. As analogues these compounds can interfere in nucleic acid synthesis or block nucleosides- and/or nucleotide-dependent biological processes by mimicking natural nucleosides and serving as inhibitors or building units [9][10

TEMPO-derived spin labels linked to the nucleobases adenine and cytosine for probing local structural perturbations in DNA by EPR spectroscopy

• Dnyaneshwar B. Gophane and
• Snorri Th. Sigurdsson

Beilstein J. Org. Chem. 2015, 11, 219–227, doi:10.3762/bjoc.11.24

• -shape analysis of the EPR spectra [64][65][66][67][68][69][70][71][72][73]. The spin labels for such experiments are attached to the nucleotide via a flexible or a semi-flexible tether, which allows some motion of the spin label independent of the nucleic acid. Spin-label motion is affected by the local

Synthesis of divalent ligands of β-thio- and β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase

• María Emilia Cano,
• Rosalía Agusti,
• Alejandro J. Cagnoni,
• María Florencia Tesoriero,
• José Kovensky,
• María Laura Uhrig and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 3073–3086, doi:10.3762/bjoc.10.324

• -galactopyranosides (βGalp) present in T. cruzi mucins play an important role in the interaction between the parasite and the host since they are the acceptors for sialic acid transferred by the unique trans-sialidase (TcTS) [7][8][9] from host cells instead of using a sialyltransferase and the donor nucleotide CMP

A comparative study of the interactions of cationic hetarenes with quadruplex-DNA forming oligonucleotide sequences of the insulin-linked polymorphic region (ILPR)

• Darinka Dzubiel,
• Heiko Ihmels,
• Mohamed M. A. Mahmoud and
• Laura Thomas

Beilstein J. Org. Chem. 2014, 10, 2963–2974, doi:10.3762/bjoc.10.314

• a has the highest transcriptional activity [2][3]. It was shown that the sequences a–c form stable G-quadruplex structures in vitro and that this tendency is even enhanced by binding of the insulin protein [4][5][6][7][8]. In addition, it was demonstrated that the nucleotide sequence a2, [d

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

• instance, adenine derivative 15 (Figure 6) selectively recognized the complementary nucleotide (UMP) by specific change in the UV–vis spectrum of phenanthridine subunits and high affinity [75]. Molecular modelling studies proposed a structure of the 15–UMP complex stabilized by a set of intra- and

Versatile synthesis of amino acid functionalized nucleosides via a domino carboxamidation reaction

• Vicky Gheerardijn,
• Jos Van den Begin and
• Annemieke Madder

Beilstein J. Org. Chem. 2014, 10, 2566–2572, doi:10.3762/bjoc.10.268

• information. Only recently, the use of synthetic oligonucleotides and their modified analogues for a range of therapeutic and diagnostic purposes [1], including antisense therapy [2][3], antigene therapy [4][5] and SNP (Single Nucleotide Polymorphism) detection [6] has gained major interest. Due to their

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

• nucleotide opposite an AEGIS nucleotide by (a) not being provided the complementary AEGIS triphosphate and (b) exploiting a chemical feature of the AEGIS nucleotide that directs a specific mismatch. For example, when the AEGIS nucleotide 2’-deoxy-5-methylisocytidine (trivially designated S) and its AEGIS

• nucleotide overlap with melting temperatures predicted to lie in a narrow range (44–56 °C; calculated without magnesium). OligArch also designed the sequences to have no-off target hybrids having a melting temperature greater than 25 °C, a full 20 °C below that predicted for the desired annealing pairs. Two

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

• Lenka Postova Slavetinska Dominik Rejman Radek Pohl Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic 10.3762/bjoc.10.205 Abstract Conformational preferences of the pyrrolidine ring in nucleotide analogs

• 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

• successful approach in developing antiviral therapeutics. Our long-term interest in the synthesis and evaluation of biological properties of phosphonate azanucleotides has yielded several potent inhibitors of nucleoside/nucleotide metabolizing enzymes: thymine derivatives 4 and 11 (Figure 1 and Figure 2

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

• has been replaced by a charge neutral peptide backbone, such as the peptide nucleic acids (PNAs) [15] or by a nucleotide derived phosphorodiamidate backbone, such as the morpholino oligonucleotides (PMOs) [16]. Of particular interest is the class of conformationally constrained oligonucleotides

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

• 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

• strengths of the G:C and A:T pair. Adding two additional nucleotides increases the number of potential hybridizing 15mers to 470 billion (≈ 615), nearly 500 fold higher. Adding four AEGIS nucleotides increases this number to 35 trillion (≈ 815). With a full AEGIS alphabet containing 12 nucleotide letters

• application will ensure that the nucleotide sequence is completely unchanged in the reassembled sequence. Finally, short “non-changeable” regions (such as restriction enzyme recognition sites) can be entered to ensure no AEGIS substitutions occur at these locations. User interface Using OligArch’s web-based

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

• present results can be very useful in the design of new probes for single point mutations and single nucleotide polymorphisms (SNPs), highly relevant in the genomic as well as in the clinical fields. Experimental General information Reagents were purchased from Sigma-Aldrich, Fluka, Merck, Carlo Erba, TCI

Design, automated synthesis and immunological evaluation of NOD2-ligand–antigen conjugates

• Marian M. J. H. P. Willems,
• Gijs G. Zom,
• Nico Meeuwenoord,
• Ferry A. Ossendorp,
• Herman S. Overkleeft,
• Gijsbert A. van der Marel,
• Jeroen D. C. Codée and
• Dmitri V. Filippov

Beilstein J. Org. Chem. 2014, 10, 1445–1453, doi:10.3762/bjoc.10.148

• that conjugates, in which Pam3CSK4 or CpG DNA were incorporated, showed an increased uptake of conjugated peptide. Increased DC maturation and enhanced antigen presentation was achieved in comparison to the mixture of the single peptide and ligands [13][14]. In the late 1990s the cytosolic nucleotide

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

• steric effects [31]. The strategy is based on the finding that certain PEGylated nucleotide-sugars are effectively transferred to a glycan acceptor by the corresponding glycosyltransferase. A modified sialic acid PEGylated at the 5’-amino position in the CMP nucleotide (CMP-SA-5-NHCOCH2NHPEG) can be

• catalyzed by CMP-sialic acid synthetase, the nucleotide is deprotected and the free amine is utilized as a locus to PEG attachment. The introduction of the PEGylated sialic acid into the glycoprotein takes place in two steps. First, an O-glycan is introduced enzymatically and second, PEGylated sialic acid

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

• shown for hydroquinone in Scheme 24 [76]. O,O-dialkyl thiophosphite was also engaged in AT reactions to produce dinucleotide designed as an anti-HIV prodrug [77]. H-phosphonothioates are intermediates considered for the synthesis of nucleotide analogues. This functional group can be used as a