DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies

• Yongdong Su,
• Maitsetseg Bayarjargal,
• Tracy K. Hale and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2021, 17, 749–761, doi:10.3762/bjoc.17.65

• modifications were introduced into the DNA backbone using the Staudinger reaction between the 3’,5’-dinucleoside β-cyanoethyl phosphite triester formed during DNA synthesis and sulfonyl azides, 4-(azidosulfonyl)-N,N,N-trimethylbutan-1-aminium iodide (N+ azide) or p-toluenesulfonyl (tosyl or Ts) azide, to

• provide either a zwitterionic phosphoramidate with N+ modification or a negatively charged phosphoramidate for Ts modification in the DNA sequence. The incorporation of these N+ and Ts modifications led to the formation of thermally stable parallel DNA triplexes, regardless of the number of modifications

• incorporated into the oligodeoxynucleotides (ONs). For both N+ and Ts-modified ONs, the antiparallel duplexes formed with complementary RNA were more stable than those formed with complementary DNA (except for ONs with modification in the middle of the sequence). Additionally, the incorporation of N

Synthesis and properties of oligonucleotides modified with an N-methylguanidine-bridged nucleic acid (GuNA[Me]) bearing adenine, guanine, or 5-methylcytosine nucleobases

• Naohiro Horie,
• Takao Yamaguchi,
• Shinji Kumagai and
• Satoshi Obika

Beilstein J. Org. Chem. 2021, 17, 622–629, doi:10.3762/bjoc.17.54

• for the guanidine moiety because it can be easily removed under the basic conditions (ammonia/methylamine solution) used for the DNA synthesis [20]. The phosphoramidite synthesis was started from 2'-amino-LNAs 1a–c, which were rapidly prepared via the transglycosylations of 2'-amino-LNA-T [25]. First

• the middle position of 12-mer oligonucleotides (Table 1). The oligonucleotide synthesis was performed using an automated DNA synthesizer following the established synthetic method for GuNA[Me]-T-modified oligonucleotides [20]. 5-(Ethylthio)-1H-tetrazole (ETT) was used as an activator for the coupling

• , and the coupling time was extended from 40 s to 20 min for the GuNA[Me] phosphoramidites. Other conditions were the same as those used for general DNA synthesis. After the elongation, the oligonucleotides were treated with ammonia/methylamine solution (7 M NH3 in methanol/40% aqueous methylamine 1:1

Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

• Marek Kõllo,
• Marje Kasari,
• Villu Kasari,
• Tõnis Pehk,
• Ivar Järving,
• Margus Lopp,
• Arvi Jõers and
• Tõnis Kanger

Beilstein J. Org. Chem. 2021, 17, 581–588, doi:10.3762/bjoc.17.52

• IDT codon optimization tool (to eliminate rare codons). Synthetic DNA was ordered from Twist Bioscience and inserted into pET21a backbone as one operon (see Supporting Information File 2) under the control of an IPTG-inducible tac promoter. The obtained plasmid was verified by DNA sequencing. To

• Supporting Information File 201: General material and methods for the construction of the biocatalyst as well as NMR spectra of synthesized compounds. Supporting Information File 202: DNA sequence. Funding The authors thank the Estonian Ministry of Education and Research (Grant Nos. PRG657 and PRG1031) and

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• packing effect has an implication on the thermostability of the triple helix [35][98][99]. In another study, fluoroprolines were incorporated in KlenTag DNA polymerase from a thermophilic organism, Thermus aquaticus [119]. The expression of the target protein was only observed with R-Flp, but not with S

• subdomain [129], T. thermohydrosulfuricus lipase [130][131][132], human ubiquitin [133], single-chain Fv format protein [134], KlenTag DNA polymerase [135], thioredoxin A [120], β2-microglobulin [136], red fluorescent protein [137][138], Pin1 WW domain [139], bacteriophage T4 fibritin C-terminal domain [106

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• their functional architecture. Such an approach typically includes the use of a variety of high-resolution proteomic tools, cryo-electron microscopy and X-ray crystallography to achieve full molecular characterization at the atomic level. However, macromolecules such as DNA/RNA and proteins are not

• IDPs upon tertiary and quaternary complex formation [79]. The Myc-Max heterodimer is a well-known oncogenic transcription factor complex able to bind to enhancer box (E-box) regions (5’-CACGTG-3’) of DNA with low-nanomolar affinity, what triggers its biological function as a transcriptional regulator

• presence of DNA, and another intrinsically disordered binding partner, breast cancer antigen 1 (BRCA1) (Figure 12). In this work the strategy employed involved the introduction of a perfluorinated [19F]3,5‐bis(trifluoromethyl)benzyl-based tag into the single cysteine residue of Myc. This modification

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

Au(III) complexes with tetradentate-cyclam-based ligands

• Ann Christin Reiersølmoen,
• Thomas N. Solvi and
• Anne Fiksdahl

Beilstein J. Org. Chem. 2021, 17, 186–192, doi:10.3762/bjoc.17.18

• ][20][21]. Simple [Au(III)–cyclam] complexes have been investigated for various biological properties [22][23][24][25][26][27][28][29]. Particularly, studies have focused on their potential in vitro anticancer properties [24][26][29], the activity against a falciparum strain [22], the in vitro DNA

Synthesis, crystal structures and properties of carbazole-based [6]helicenes fused with an azine ring

• Daria I. Tonkoglazova,
• Anna V. Gulevskaya,
• Konstantin A. Chistyakov and
• Olga I. Askalepova

Beilstein J. Org. Chem. 2021, 17, 11–21, doi:10.3762/bjoc.17.2

• [31], chemical sensors [32], DNA-intercalators [33][34] etc. Besides typical carbohelicenes, heterohelicenes, incorporating one or more heteroaromatic units in the skeleton, have also gained increasing attention [1][2][3][4][5][6][7][8][9][10][11]. The presence of heteroatoms (S, N, O, P) in the fused

Secondary metabolites of Bacillus subtilis impact the assembly of soil-derived semisynthetic bacterial communities

• Heiko T. Kiesewalter,
• Carlos N. Lozano-Andrade,
• Mikael L. Strube and
• Ákos T. Kovács

Beilstein J. Org. Chem. 2020, 16, 2983–2998, doi:10.3762/bjoc.16.248

• , whereas the remaining five were supplemented with respective B. subtilis strains by adding 10% of the final volume. The cultures were incubated at 21–23 °C and 250 rpm for 48 h. DNA was extracted from two replicates of the initial soil sample, the 12 h precultivated soil suspensions and the B. subtilis

• -treated or untreated mock communities cocultivated for 48 h. DNA extraction Environmental- and semisynthetic-community genomic DNA was extracted from either 250 mg soil or 250 µL bacterial culture, respectively, by using the DNeasy PowerSoil Pro Kit (QIAGEN) and following the manufacturer’s instructions

• . Amplification of 16S rRNA hypervariable regions V3-V4 The V3-V4 region of the 16S rRNA gene was PCR-amplified from the extracted DNA samples using Fw_V3V4 (5’-CCTACGGGNGGCWGCAG-3’) and Rv_V3V4 (5’-GACTACHVGGGTATCTAATCC-3’) primers that were tagged with short barcodes with a length of eight nucleotides, listed

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• enhanced and blue-shifts after affinity/recognition in a polar solvent. Several computational studies confirmed that the spectral change is caused by the insertion of the environment-sensitive fluorophore in the hydrophobic domains/grooves of the target protein/DNA (Figure 1A). The major problem of these

• important biomolecules including nucleotides, DNA, proteins, lipids etc. in aqueous media. Fluorescent peptides have also been used for specific organelles such as lysosomes tracking. In this review, it is summarized Schmuck group’s tremendous effort in developing fluorescent peptide-based probes for

• interacts effectively with double-stranded DNA (dsDNA) as positively charged lysine residues are expected to interact with the phosphate backbone electrostatically. Upon binding to dsDNA, it undergoes a conformational change from the folded to an extended form that switches the fluorescence signal from

Synthesis of imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes

• Dmitrii A. Aksenov,
• Nikolai A. Arutiunov,
• Vladimir V. Maliuga,
• Alexander V. Aksenov and
• Michael Rubin

Beilstein J. Org. Chem. 2020, 16, 2903–2910, doi:10.3762/bjoc.16.239

• imidazo[1,5-a]pyridine core is also considered to be one of the privileged pharmacophoric scaffolds and can be found in many biologically active compounds, for example, the potent antitumor agent C 1311 inhibiting topoisomerase II [4][5][6][7][8][9] or pirmagrel, a cytotoxic immunosuppressant and DNA

Incorporation of a metal-mediated base pair into an ATP aptamer – using silver(I) ions to modulate aptamer function

• Marius H. Heddinga and
• Jens Müller

Beilstein J. Org. Chem. 2020, 16, 2870–2879, doi:10.3762/bjoc.16.236

• function opens new possibilities for applications of oligonucleotides. Keywords: aptamer; ATP; bioinorganic chemistry; DNA; imidazole; metal-mediated base pairs; Introduction Aptamers are oligonucleotides capable of recognizing and binding to specific molecules up to the size of proteins [1]. While

• (or removal) of external triggers, allowing to switch the nucleic acid function [8]. For example, DNA can be used in nanotechnology to create mechanically moving systems such as walkers, fueled by the addition of appropriately designed oligonucleotides [9]. Moreover, external triggers can be applied

• to release a DNA-bound cargo (in the form of small organic molecules) [10]. Similarly, metal ions can trigger DNA folding into a catalytically active topology [11][12]. Metal-mediated base pairs are artificial base pairs in which hydrogen bonds between the complementary nucleobases are formally

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• functions, for instance, to control the biological processes that eventually sustain life on our planet [1]. A well-known example is the storage of an immense amount of information in the DNA, using the algorithm of base pairing (AT and GC) between the heterocycles adenine (A), thymine (T), guanine (G) and

Synthesis and investigation of quadruplex-DNA-binding, 9-O-substituted berberine derivatives

• Jonas Becher,
• Daria V. Berdnikova,
• Heiko Ihmels and
• Christopher Stremmel

Beilstein J. Org. Chem. 2020, 16, 2795–2806, doi:10.3762/bjoc.16.230

• examined with photometric and fluorimetric titrations, thermal DNA denaturation analysis, and CD spectroscopy. The results from the spectrometric titrations indicated the formation of 2:1 or 1:1 complexes (ligand:G4-DNA) with log Kb values of 10–11 (2:1) and 5–6 (1:1), which are typical for berberine

• derivatives. Notably, a clear relationship between the binding affinity of the ligands with the length of the alkyl linker chain, n, was not observed. However, depending on the structure, the ligands exhibited different effects when bound to the G4-DNA, such as fluorescent light-up effects and formation of

• ICD bands, which are mostly pronounced with a linker length of n = 4 (with a2) and n = 5 (with 22AG), thus indicating that each ligand–G4-DNA complex has a specific structure with respect to relative alignment and conformational flexibility of the ligand in the binding site. It was shown exemplarily

Encrypting messages with artificial bacterial receptors

• Pragati Kishore Prasad,
• Naama Lahav-Mankovski,
• Leila Motiei and
• David Margulies

Beilstein J. Org. Chem. 2020, 16, 2749–2756, doi:10.3762/bjoc.16.225

• receptors is described. We show that the binding of DNA-based artificial receptors to E. coli expressing His-tagged outer membrane protein C (His-OmpC) induces a Förster resonance energy transfer (FRET) between the dyes, which results in the generation of a unique fluorescence fingerprint. Because the

• cell surface proteins with self-assembled synthetic receptors based on modified DNA duplexes [2] (Figure 1A). One of the oligodeoxynucleotides (ODNs) constituting the artificial receptors (ODN-1) is appended with a trinitrilotriacetic acid group (tri-NTA) that was developed by our group [3] and can

• the bacteria was obtained by incubating them with the DNA-based receptors (Figure 1) and washing off the excess of unbound receptors. The super resolution fluorescent images revealed that the bacterial membrane was densely covered [2]. Although this approach was used to label bacteria with different

Selective recognition of ATP by multivalent nano-assemblies of bisimidazolium amphiphiles through “turn-on” fluorescence response

• Rakesh Biswas,
• Surya Ghosh,
• Shubhra Kanti Bhaumik and
• Supratim Banerjee

Beilstein J. Org. Chem. 2020, 16, 2728–2738, doi:10.3762/bjoc.16.223

• [20][21]. A number of elegant examples of self-assembled multivalent systems targeting biological analytes such as DNA, heparin, proteins, carbohydrates, etc. have been reported in the literature [22][23][24][25][26][27]. ATP is an important bio-anion that is the energy currency in cells and is

Optical detection of di- and triphosphate anions with mixed monolayer-protected gold nanoparticles containing zinc(II)–dipicolylamine complexes

• Lena Reinke,
• Julia Bartl,
• Marcus Koch and
• Stefan Kubik

Beilstein J. Org. Chem. 2020, 16, 2687–2700, doi:10.3762/bjoc.16.219

• surface plasmon resonance of the individual AuNPs starts to couple when they approach each other [7][8][9]. Early examples of optical probes working in this way are the nanoparticles introduced by Mirkin et al., containing immobilized oligonucleotides that aggregated in the presence of single-stranded DNA

Tools for generating and analyzing glycan microarray data

• Akul Y. Mehta,
• Jamie Heimburg-Molinaro and
• Richard D. Cummings

Beilstein J. Org. Chem. 2020, 16, 2260–2271, doi:10.3762/bjoc.16.187

• structural informatics tools. Keywords: data analysis; glycan binding; glycan microarray; glycomics; informatics; Introduction Glycans represent a major type of biomolecule in all living things, along with DNA, RNA, lipids and proteins [1]. In mammals, glycans commonly occur as post-translational

• intricacies involved at multiple levels. Unlike DNA and proteins, glycans are neither linear nor template driven, making their structures computationally taxing. In addition, the complexity is compounded by the sample and experimental meta data associated with the glycan microarray experiment. The following

Naphthalene diimide bis-guanidinio-carbonyl-pyrrole as a pH-switchable threading DNA intercalator

• Poulami Jana,
• Filip Šupljika,
• Carsten Schmuck and
• Ivo Piantanida

Beilstein J. Org. Chem. 2020, 16, 2201–2211, doi:10.3762/bjoc.16.185

• naphthalene diimde analogue (NDI) equipped at the imide positions with two guanidinio-carbonyl-pyrrole (GCP) pendant arms interacted significantly stronger with ds-DNA at pH 5 than at pH 7, due to reversible protonation of the GCP arms. This was consequence of a pH-switchable threading intercalation into ds

• -DNAs only at pH 5, while at neutral conditions (pH 7) NDI-GCP2 switched to the DNA minor groove binding. Intriguingly, NDI-GCP2 was at both pH values studied bound to the ds-RNA major groove, still showing a higher affinity and thermal denaturation effect at pH 5 due to GCP protonation. At excess over

• the DNA/RNA conjugate NDI-GCP2 showed also aggregation along the ds-polynucleotide and AFM and DLS demonstrated that NDI-GCP2 has pronounced ds-DNA condensation ability. Keywords: AFM; circular dichroism; DNA/RNA recognition; fluorescence; guanidinio-carbonyl-pyrrole; naphthalene diimide

Muyocopronones A and B: azaphilones from the endophytic fungus Muyocopron laterale

• Ken-ichi Nakashima,
• Junko Tomida,
• Tomoe Tsuboi,
• Yoshiaki Kawamura and
• Makoto Inoue

Beilstein J. Org. Chem. 2020, 16, 2100–2107, doi:10.3762/bjoc.16.177

• elucidation, and antimicrobial activity evaluation are described. Results and Discussion Muyocopron laterale ECN279 was isolated from a healthy leaf of Canavalia lineata and identified by sequencing the D1/D2 26S rRNA gene and the internal transcript spacers (ITS) of ribosomal DNA [16]. In a similar manner as

• Technologies). DNA sequencing was performed using an Applied Biosystems 3130 genetic analyzer. Silica gel AP-300 (Toyota Kako) was employed for column chromatography (CC). Silica gel 60 F254 and RP-18 F254S (both Merck) were used for TLC. Fungal material and identification Muyocopron laterale ECN279 was

• isolated from a healthy leaf of Canavalia lineata (Thunb.) DC collected at Tanegashima, Kagoshima, Japan. Strain isolation was performed using a previously described method [13]. Based on the DNA sequencing of the rDNA ITS and the D1/D2 domain of the 26S rDNA, the isolate was identified as Muyocopron

Naphthalene diimide–amino acid conjugates as novel fluorimetric and CD probes for differentiation between ds-DNA and ds-RNA

• Annike Weißenstein,
• Myroslav O. Vysotsky,
• Ivo Piantanida and
• Frank Würthner

Beilstein J. Org. Chem. 2020, 16, 2032–2045, doi:10.3762/bjoc.16.170

• interacted with ds-DNA/RNA by threading intercalation. Different from a reference NDI dye with identical visible range absorbance (520–540 nm) and Stokes shifts in emission (+60 nm, quantum yield > 0.2), only these amino acid–NDI conjugates showed selective fluorimetric response for GC-DNA in respect to AT(U

• )-polynucleotides. The DNA/RNA binding-induced circular dichroism (ICD) response of NDI at 450–550 nm strongly depended on the length and rigidity of the linker to the amino acid unit, which controls the orientation of the NDI unit inside within the intercalative binding site. The ICD selectivity also depends on

• the type of polynucleotide, thus the studied NDI dyes act as dual fluorimetric/ICD probes for sensing the difference between here used GC-DNA, AT-DNA and AU-RNA. Keywords: amino acid–fluorophore conjugate; circular dichroism; DNA/RNA recognition; fluorescence; intercalation; naphthalene diimide

Automated high-content imaging for cellular uptake, from the Schmuck cation to the latest cyclic oligochalcogenides

• Rémi Martinent,
• Javier López-Andarias,
• Dimitri Moreau,
• Yangyang Cheng,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2020, 16, 2007–2016, doi:10.3762/bjoc.16.167

• more stable complexes 12 with the phosphodiesters in the DNA backbone, and thus making it possible to transfect cells with shorter peptides. In 2015, the Schmuck group reported the first example of a small peptide with only four amino acids for gene transfection [27]. The binding affinity of 13 to DNA

• an endosomal pathway. The low pKa value of the four GCP moieties could result in an improved buffering capacity, which could facilitate endosomal escape by the proton-sponge effect [28]. Significant inhibition of DNA transfection by bafilomycin (a macrolide antibiotic that can block the endosomal

• on the endosomal uptake and release. However, a better binding affinity to DNA does not necessarily mean a higher DNA transfection efficiency. As an example, two GCP-modified peptide tweezers 14 with nanomolar dissociation constants, identified by the high-throughput screening of a combinatorial

Nonenzymatic synthesis of anomerically pure, mannosyl-based molecular probes for scramblase identification studies

• Giovanni Picca,
• Markus Probst,
• Simon M. Langenegger,
• Oleg Khorev,
• Peter Bütikofer,
• Anant K. Menon and
• Robert Häner

Beilstein J. Org. Chem. 2020, 16, 1732–1739, doi:10.3762/bjoc.16.145

• into stereodefined, anomeric phosphoramidite derivatives. The method is based on adapted procedures developed for DNA solid-phase synthesis [17]. Phosphoramidite chemistry allows the connection of two molecular entities via a phosphodiester linkage and was found to be perfectly suited for this purpose

Models of necessity

• Timothy Clark and
• Martin G. Hicks

Beilstein J. Org. Chem. 2020, 16, 1649–1661, doi:10.3762/bjoc.16.137

• conformation, reactivity and structure, for example in the determination of the structure of DNA [42]. In inorganic chemistry, the standard Lewis eight-electron picture is complemented by the VSEPR (Valence Shell Electron Pair Repulsion) or Gillespie–Nyholm model [43], which gives rise to a series of standard

Synthesis of new dihydroberberine and tetrahydroberberine analogues and evaluation of their antiproliferative activity on NCI-H1975 cells

• Giacomo Mari,
• Lucia De Crescentini,
• Serena Benedetti,
• Francesco Palma,
• Stefania Santeusanio and
• Fabio Mantellini

Beilstein J. Org. Chem. 2020, 16, 1606–1616, doi:10.3762/bjoc.16.133

• activity [13][14][15][16][17][18][19], and an increased DNA and RNA binding efficacy [4][6][9], due to its aromatic interactions with the biological macromolecules [20]. Another interesting and promising derivative is dihydroberberine (DHBER), the reduced form of BER. The enaminic function of this alkaloid