Organic chemistry meets polymers, nanoscience, therapeutics and diagnostics

• Vincent M. Rotello

Beilstein J. Org. Chem. 2016, 12, 1638–1646, doi:10.3762/bjoc.12.161

• nanocomposite materials, including regular structures using diblock copolymers [25][26] and nanoparticle–protein [27][28] and nanoparticle–nucleic acid composites [29]. Concurrently with our 3D self-assembly, we pursued the use of nanoparticles for surface modification. This research has focused on the use of

Nucleic acids through condensation of nucleosides and phosphorous acid in the presence of sulfur

• Tuomas Lönnberg

Beilstein J. Org. Chem. 2016, 12, 670–673, doi:10.3762/bjoc.12.67

• elemental sulfur. Desulfurization and subsequent digestion of the products by P1 nuclease revealed that nearly 80% of the internucleosidic linkages thus formed were of the canonical 3´,5´-type. Keywords: H-phosphonate; nucleic acid; polymerization; phosphite; sulfurization; Introduction Arguably the most

• nucleic acid polymerizations described so far have utilized activated starting materials, such as cyclic phosphates [1][2] or phosphoroimidazolides [3][4]. The trivalent phosphorus atom of phosphorous acid is much more susceptible to a nucleophilic attack than the pentavalent phosphorus atom of phosphoric

Learning from the unexpected in life and DNA self-assembly

• Jennifer M. Heemstra

Beilstein J. Org. Chem. 2015, 11, 2713–2720, doi:10.3762/bjoc.11.292

• faculty members on my thesis committee to be Profs. Steve Zimmerman and Scott Silverman, who are both leaders in the field of nucleic acid molecular recognition. As my graduation neared, Jeff, Steve, and Scott all enthusiastically encouraged me to pursue postdoctoral research and then a career in academia

• absence of cocaine, but in the presence of varying concentrations of sodium chloride, as increasing ionic strength increases the enthalpic gain for nucleic acid duplex formation [10]. We found that the ligation yield consistently increased with increasing ionic strength, which served as an initial

• key to understanding and engineering the complex molecular architectures of aptamer-based sensors. The common thread that is woven throughout our research program is the utilization of nucleic acid molecular recognition and self-assembly to generate functional architectures for biosensing and

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• alkaloids such as meridine (56) that are found to exert its antifungal activity via the inhibition of nucleic acid biosynthesis [87]. Petrosamine B (99), isolated from the sponge Oceanapia sp., inhibited the Helicobacter pylori enzyme aspartyl semialdehyde dehydrogenase explaining it as an antibacterial

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

• within the cis and the trans compartment, which is due to the fact that the polyanionic nucleic acid is unable to cross the artificial bilayer. Figure 10 shows the bilayer brightness vs the various events for the lipo-oligonucleotide 14. This oligomer carries a phytyl residue at the N(3) atom of 5

• the semi-minor axis, b, of a hydrated nucleic acid single strand is 12.03 ± 0.15 Å. The frictional coefficient, f, of an ellipsoid, moving at random, with the semi-major axis a and semi-minor axis b [20], is described by Equation 1: Figure 16 schematically displays the structure of a Cy5-labeled lipo

• environment, water molecules form a hydration shell around the nucleic acid. Consequently, the surface of the nucleic acid chain is smoothed, and the partial volume of the hydrated molecule (Vhyd) is increased by the volume of the water shell. By determining the Vhyd of the LONs, one can calculate the degree

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

• oligomeric interactions involving multiple carbohydrate units. In efforts to recapitulate the diverse spatial arrangements of the carbohydrate units, assemblies based on hybridization of nucleic acid conjugates have been used to display simplified ligands with tailored interligand distances and valences. The

• programmability of the assemblies lends itself to a combinatorial display of multiple ligands. Recent efforts in the synthesis and applications of such conjugates are discussed. Keywords: glycan; glycoconjugate; DNA display; multivalency; nucleic acid conjugates; oligomeric interaction; Introduction Cell

• 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

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

• surroundings of a nucleic acid groove can be detected with spin labels by EPR spectroscopy. Here, we describe the use of an analogous derivative of A, namely TA, in which a TEMPO moiety is conjugated to the exocyclic amino group of 2´-deoxyadenosine (Figure 1B), to study local perturbations for a purine base

NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A–T phosphoramidite building blocks

• Boris Schmidtgall,
• Claudia Höbartner and
• Christian Ducho

Beilstein J. Org. Chem. 2015, 11, 50–60, doi:10.3762/bjoc.11.8

• Biophysical Chemistry, Am Fassberg 11, 37 077 Göttingen, Germany Department of Chemistry, Institute of Organic and Biomolecular Chemistry, Georg-August-University Göttingen, Tammannstr. 2, 37 077 Göttingen, Germany 10.3762/bjoc.11.8 Abstract Modifications of the nucleic acid backbone are essential for the

• to develop oligonucleotide-based drug candidates or biomedical chemical probes [5][6]. Native nucleic acids are connected by phosphate diesters as linking units, thus leading to a polyanionic backbone structure. Implications of this characteristic feature of nucleic acid architecture have been

• discussed by Westheimer [7] and Benner [8][9], among others. However, the accumulation of negative charges in the nucleic acid backbone is mainly responsible for their limited membrane penetration. Consequently, a significant number of artificial internucleotide linkages has been studied with the aim to

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

• neomycin–methidium conjugate 16 (Figure 7) [80], which selectively recognized the DNA:RNA hybrid duplex (poly(dA):poly(rU)) with sub-nanomolar affinity, much higher than the affinities shown for traditional aminoglycoside–nucleic acid targets. This joins the mentioned EB analogue to a small number of

Nucleic acid chemistry

• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2014, 10, 2928–2929, doi:10.3762/bjoc.10.311

• runs automatically on machines, so-called DNA synthesizers. With special care during each synthesis step, even longer oligonucleotides can be prepared in a similar, almost routine fashion. The field of nucleic acid chemistry has exploded: natural and artificial functionalities, as well as probes

• cases, postsynthetic strategies can allow for the desired oligonucleotides modification. This becomes an even more important issue for functionalities, probes or biologically relevant molecules that are incompatible with routine phosphoramidite chemistry. Although nucleic acid chemistry appears to be a

• mature part of organic and bioorganic chemistry, the many questions that are still being raised by research in biology and chemical biology give sufficient motivation to continue to synthesize new nucleic acid probes and thereby further develop nucleic acid chemistry. Moreover, in addition to their

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

• increased attention for incorporation in modified nucleic acid structures both for the design of aptamers with enhanced binding properties as well as the construction of catalytic DNA and RNA. As a shortcut alternative to the incorporation of multiple modified residues, each bearing one extra functional

• additional functional groups can lead to even higher activities and selectivities. Indeed, people have realized that equipping the nucleic acid scaffold with protein side chain-like moieties may assist in the design of a broad scope of functionalized oligonucleotides with various characteristics. This can be

• groups for later incorporation into nucleic acid duplexes via solid phase DNA synthesis [33]. Results and Discussion As mentioned earlier, a number of research groups have used the SELEX or in vitro selection protocol for the incorporation of amino acid-like modifications into DNA or RNA where there is

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

• should exist which can only be shielded by solvation of the lipid head groups and of the nucleic acid phosphodiester groups as well as by the metal cations of the surrounding buffer. The supramolecular assembly of all reaction partners might look like as shown in Figure 9. From this figure it can be

• deduced that two different tilt angles (θ1 and θ2) probably exit between the bilayer surface and the double helical part (θ1) as well as between the single stranded sequence and the surface (θ2). A stretched-out, parallel association of the full length nucleic acid with the bilayer surface can be most

• which could not be observed. It is, however, obvious that a severe disturbance of either the complex formation between the probe lipo-oligonucleotide 4 and the target nucleic acid 9 and/or the intercalation of the Sybr Green dye by the overhang take place. This might be the reason for the instability of

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

• determined from the maximum of the first derivative and checked graphically by the tangent method [26]. The ΔTm values were calculated by subtracting Tm of the free nucleic acid from Tm of the complex. Every reported ΔTm value was the average of at least two measurements. The error of ΔTm is ±0.5 °C. Changes

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

• , pyrrolidinyl peptide nucleic acid (acpcPNA) was labeled at its backbone with Nile red, a solvatochromic benzophenoxazine dye, by means of click chemistry. The optical properties of the Nile red-labeled acpcPNA were investigated by UV–vis and fluorescence spectroscopy in the absence and in the presence of DNA

• – has also been incorporated into DNA as a base replacement, again without showing significant structure-induced fluorescence change [22]. Peptide nucleic acid or PNA is an electrostatically neutral analogue of DNA which can form very stable duplexes with DNA and RNA in a highly sequence specific

Second generation silver(I)-mediated imidazole base pairs

• Susanne Hensel,
• Nicole Megger,
• Kristina Schweizer and
• Jens Müller

Beilstein J. Org. Chem. 2014, 10, 2139–2144, doi:10.3762/bjoc.10.221

• functional moieties have been introduced into various nucleic acid building blocks, including, for example, modified nucleobases and modified sugar entities. A recent addition is the application of ligand systems as nucleobases surrogates [5][6][7][8][9]. In the presence of suitable transition metal ions, so

• increased charge transfer capability [10][11] and DNA-based logic gates [12][13]. Applying the concepts of coordination chemistry, a wide range of metal-specific ligands have been incorporated successfully into nucleic acids and nucleic acid derivatives. Most recently, even coordination patterns of the [2

• + 1] type could be obtained [14][15]. While most examples focus on the use of DNA, other systems such as RNA [16], GNA [17][18] (glycol nucleic acid), PNA [19][20][21], and other nucleic acid derivatives [22] have been modified as well. It is interesting to note that metal-mediated base pairs do not

Synthesis of phosphoramidites of isoGNA, an isomer of glycerol nucleic acid

• Keunsoo Kim,
• Venkateshwarlu Punna,
• Phaneendrasai Karri and
• Ramanarayanan Krishnamurthy

Beilstein J. Org. Chem. 2014, 10, 2131–2138, doi:10.3762/bjoc.10.220

• Keunsoo Kim Venkateshwarlu Punna Phaneendrasai Karri Ramanarayanan Krishnamurthy Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Rd, La Jolla, CA 92037, USA 10.3762/bjoc.10.220 Abstract IsoGNA, an isomer of glycerol nucleic acid GNA, is a flexible (acyclic

• ) nucleic acid with bases directly attached to its linear backbone. IsoGNA exhibits (limited) base-pairing properties which are unique compared to other known flexible nucleic acids. Herein, we report on the details of the preparation of isoGNA phosphoramidites and an alternative route for the synthesis of

• nucleic acids; isoGNA; oligonucleotides; phosphoramidites; Introduction Acyclic nucleic acids have garnered a lot of attention and are becoming an important component in nucleic acid chemistry [1][2][3]. Lately, there has been an explosion in the number of investigated candidates [4][5][6][7]. We have

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

• , for example, used in a conformational analysis of the prolyl ring in aminoethylprolyl peptide nucleic acid monomers [13], or in a conformational analysis of 2’-fluoro-4’-thioarabinothymidine [14]. The performance of the Matlab Pseudorotation GUI program was tested on two 4’-thio-2’deoxynucleoside

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

• - and tc-DNA have been conceived to reduce the entropy upon duplex formation with a nucleic acid target by reducing the conformational flexibility around the C3’–C4’ and C4’–C5’ bonds, while achieving as much as possible of a geometric match with the backbone conformation of DNA in duplexed form. From

• structure/nucleic acid affinity profile of this modification we also became interested in nucleoside 11β, containing a double bond instead of the cyclopropane ring. In the context of oligonucleotides this derivative seemed appropriate to investigate the direct steric influence of the cyclopropyl/methylene

• the context of nucleic acid duplex conformation. Quite interestingly, the original tc-T nucleoside [34], for which we solved the X-ray structure here for the first time (Figure 2), shows considerable conformational variability in the furanose part. The asymmetric unit contains two independent

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

• 7, 14183, Huddinge, Sweden 10.3762/bjoc.10.154 Abstract Pyrene derivatives can be incorporated into nucleic acid analogs in order to obtain switchable probes or supramolecular architectures. In this paper, peptide nucleic acids (PNAs) containing 1 to 3 1-pyreneacetic acid units (PNA1–6) with a

• recognition; triplex stabilization; Introduction Peptide nucleic acid (PNA) probes are very selective in the recognition of DNA and have been used in a large variety of diagnostic methods, easily allowing the detection of point mutations at very low concentrations [1][2][3]. Poly-pyrimidine PNA can form very

Molecular recognition of surface-immobilized carbohydrates by a synthetic lectin

• Melanie Rauschenberg,
• Eva-Corrina Fritz,
• Christian Schulz,
• Tobias Kaufmann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 1354–1364, doi:10.3762/bjoc.10.138

• of carbohydrates in cell biology is still lagging far behind our knowledge of proteins and nucleic acids. This backlog is mainly due to the complexity of biological carbohydrates. Additionally, established analytical and synthetic methods in protein and nucleic acid research such as automated

Synthesis, characterization and DNA interaction studies of new triptycene derivatives

• Sourav Chakraborty,
• Snehasish Mondal,
• Rina Kumari,
• Sourav Bhowmick,
• Prolay Das and
• Neeladri Das

Beilstein J. Org. Chem. 2014, 10, 1290–1298, doi:10.3762/bjoc.10.130

• per the manufacturer’s yield report. Calf thymus DNA (ctDNA), ethidium bromide (EtBr), chemicals for buffer preparation and synthesis were purchased from Sigma-Aldrich or Alfa Aesar and were used as received. Sybr-Gold® nucleic acid stain was obtained from Invitrogen. Gel images were captured by

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

• 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

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

• switching of optical properties in DNA can be achieved selectively at 310 nm (forward) and 450 nm (backward); both wavelengths are outside the normal nucleic acid absorption range. Moreover, this nucleoside was proven to be photochemically stable and allows switching back and forth several times. These

• . Hence, the absorption side band at 310 nm should allow, at least in principal, the selective excitation of the switch, outside the nucleic acid absorption range. Accordingly, the photoswitching of 4 was probed at 242 and 310 nm. In fact, by irradiation at either wavelength the closed form of nucleoside

• properties of the nucleosides were evaluated and revealed that only nucleoside 4 allows selective excitation at 310 nm, outside the nucleic acid absorption window, to close the diarylethene chromophore. Switching back of the colored form of all three nucleosides 4–6 to the corresponding opened forms can be