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

4-Hydroxy-3-methyl-2(1H)-quinolone, originally discovered from a Brassicaceae plant, produced by a soil bacterium of the genus Burkholderia sp.: determination of a preferred tautomer and antioxidant activity

• Dandan Li,
• Naoya Oku,
• Yukiko Shinozaki,
• Yoichi Kurokawa and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1489–1494, doi:10.3762/bjoc.16.124

• used as a selection pressure during the initial exhaustive enrichment culture stage. The 16S rDNA sequence of strain 3Y-MMP was determined by a DNA analysis service (Tsuruga Bio, Toyobo Co. Ltd., Osaka, Japan) using a primer set 10F (5′-GTTTGATCCTGGCTCA-3′) and 800R (5′-TACCAGGGTATCTAATCC-3′). A

• partial sequence with a length of 800 bp (accession number LC508727) thus read was queried against the Basic Local Alignment Search Tool program (BLAST) available at the DNA Data Bank of Japan (DDBJ) website, which reported 99.9% homology to Burkholderia cepacia strain N1_1_43 (accession number MN691134

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• particular phenanthridines, are substructures present in a wide range of both natural and synthetic products, including trisphaeridine [12] (that exhibits an anti-HIV-I protease activity) and the antifungal sanguinarine [13]. Some phenantridinium derivatives are known as well, notably fagaronine (a DNA

• topoisomerase 1 inhibitor [14] and DNA intercalator), bicolorine (5-methyl-[1,3]dioxolo[4,5-j]phenanthridin-5-ium ion, a trypanocidal) [15], and the antimalarian nitidine, as well as ethidium bromide (EB), that has been employed as a DNA- and RNA-fluorescent marker for a long time (some examples are collected

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

• Carlos H. Escalante,
• Eder I. Martínez-Mora,
• Carlos Espinoza-Hicks,
• Alejandro A. Camacho-Dávila,
• Fernando R. Ramos-Morales,
• Francisco Delgado and
• Joaquín Tamariz

Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113

• stereoselective approaches of substrates and reagents or catalysts in a variety of processes. Examples include the substrate–enzyme recognition (the host–guest interaction) responsible for inducing pharmacological activity, the DNA-intercalation capable of generating biomolecular activity, molecular dynamics [63

Anthelmintic drug discovery: target identification, screening methods and the role of open science

• Frederick A. Partridge,
• Ruth Forman,
• Carole J. R. Bataille,
• Graham M. Wynne,
• Marina Nick,
• Angela J. Russell,
• Kathryn J. Else and
• David B. Sattelle

Beilstein J. Org. Chem. 2020, 16, 1203–1224, doi:10.3762/bjoc.16.105

• . elegans. A rich diversity of mutants is available via the Caenorhabditis Genetics Centre [91]. The discovery of RNA interference delivered via feeding worms double-stranded DNA [92] has opened the door to genome-scale gene knockdown in the search for new drug targets. These approaches can expedite the

A smart deoxyribozyme-based fluorescent sensor for in vitro detection of androgen receptor mRNA

• Ekaterina A. Bryushkova,
• Erik R. Gandalipov and
• Julia V. Nuzhina

Beilstein J. Org. Chem. 2020, 16, 1135–1141, doi:10.3762/bjoc.16.100

• different levels, including DNA, RNA, proteins, and small molecule metabolites. Today, along with other methods in clinical diagnosis biosensors are ubiquitously used in the biomedical field. The first prototype of a biosensor was invented by Leland Clark and Champ Lyons in 1962 as an amperometric Clark

• their binding capability [3] with sensitivities in the range from 1 mM for cocaine to 10 pM for Hg2+, but for many targets it averages in the 1–10 nM range [4]. Although the diversity of NAs is very large, they can be divided into DNA-based biosensors, for example, molecular beacon or TaqMan probes

• , deoxyribozyme-based biosensors [5], and aptamer-based biosensors [3]. The detection mainly relies on a specific hybridization between a well-known target fragment and the biosensor strands. To increase selectivity NAs are also created as binary or split construction. Due to the simplicity, the DNA hybridization

Cation-induced ring-opening and oxidation reaction of photoreluctant spirooxazine–quinolizinium conjugates

• Phil M. Pithan,
• Sören Steup and
• Heiko Ihmels

Beilstein J. Org. Chem. 2020, 16, 904–916, doi:10.3762/bjoc.16.82

• been shown that derivatives thereof have a great potential to serve as functional units in DNA-binding ligands [54], fluorescent dyes and chemosensors [55][56][57][58][59]. Furthermore, we have already demonstrated that styryl-substituted quinolizinium derivatives exhibit ideal photophysical and DNA

• -binding properties to be used as DNA-sensitive fluorescent probes in cell imaging [60][61][62] or as photoswitchable DNA ligands [63]. Therefore, we were interested in a combination of the photochromic properties of the spirooxazine moiety with the advantageous photophysical and biological properties of

Microwave-assisted efficient and facile synthesis of tetramic acid derivatives via a one-pot post-Ugi cascade reaction

• Yong Li,
• Zheng Huang,
• Jia Xu,
• Yong Ding,
• Dian-Yong Tang,
• Jie Lei,
• Hong-yu Li,
• Zhong-Zhu Chen and
• Zhi-Gang Xu

Beilstein J. Org. Chem. 2020, 16, 663–669, doi:10.3762/bjoc.16.63

• exhibit a wide range of biological activities, including antibiotic [8], antiviral [9], antifungal [10], phytotoxic [11], cytotoxic [12][13], and enzyme inhibitory activities against bacterial DNA-directed RNA polymerase [14]. The wide range of biological activity and structural variation of this class of

p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies

• Panagiotis S. Gritzapis,
• Panayiotis C. Varras,
• Nikolaos-Panagiotis Andreou,
• Katerina R. Katsani,
• Konstantinos Dafnopoulos,
• George Psomas,
• Zisis V. Peitsinis,
• Alexandros E. Koumbis and
• Konstantina C. Fylaktakidou

Beilstein J. Org. Chem. 2020, 16, 337–350, doi:10.3762/bjoc.16.33

• derivatives were prepared upon the reaction of the corresponding oximes with isocyanates. These novel compounds reacted photochemically in the presence of supercoiled plasmid DNA. Structure–activity relationship (SAR) studies revealed that the substituent on the imine group was not affecting the extend of the

• DNA damage, whereas the substituent of the carbamate group was critical, with the halogenated derivatives to be able to cause extensive single and double stranded DNA cleavages, acting as “synthetic nucleases”, independently of oxygen and pH. Calf thymus–DNA affinity studies showed a good-to-excellent

• studies seem to allow the prediction of the activity of derivatives able to pass intersystem crossing to their triplet energy state and thus create radicals able to damage DNA. With this study, it is shown that oxime carbamate derivatives have the potential to act as novel effective photobase generating

Two antibacterial and PPARα/γ-agonistic unsaturated keto fatty acids from a coral-associated actinomycete of the genus Micrococcus

• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku,
• Nobuyasu Matsuura,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 297–304, doi:10.3762/bjoc.16.29

• emerged on the plates, which were transferred onto a new agar medium to obtain pure isolates. One of these isolates, coded as C5-9, was identified as a member of the genus Micrococcus on the basis of 99.9% similarity in the 16S rRNA gene sequence (1395 nucleotides; DNA Data Bank of Japan/DDBJ accession

• transfected with an expression plasmid containing the ligand-binding domain of human PPARα, -β/δ, and -γ fused to the GAL4 DNA-binding domain (pPPARα–GAL4, pPPARδ–GAL4, or pPPARγ–GAL4, 0.25 µg), a luciferase reporter plasmid 17m2G TATA Luc (p17m2G, 1 µg), and the pSEAP-control vector (1 µg, Clontech, CA, USA

Absolute configurations of talaromycones A and B, α-diversonolic ester, and aspergillusone B from endophytic Talaromyces sp. ECN211

• Ken-ichi Nakashima,
• Junko Tomida,
• Takao Hirai,
• Yoshiaki Kawamura and
• Makoto Inoue

Beilstein J. Org. Chem. 2020, 16, 290–296, doi:10.3762/bjoc.16.28

• and identified by sequencing the D1/D2 26S rRNA gene and the internal transcript spacer (ITS) of its ribosomal DNA [10]. The entire mycelia, which were cultured on 300 plates of 2% malt extract agar (MEA) for 30 d, were extracted three times with MeOH at room temperature and evaporated under reduced

• diffractometers using Cu Kα radiation. DNA sequencing was performed with an Applied Biosystems 3130 genetic analyzer. Silica gel AP-300 (Toyota Kako) and Cosmosil 75C 18-OPN (Nacalai Tesque) were used for column chromatography. Silica gel 60 F254 and RP-18 F254S (both Merck) were used for TLC. Fungal material The

• leaves of Selaginella tamariscana (Selaginellaceae) were cultivated in Tajimi City, Gifu, Japan. The methods of isolation and identification of endophytic fungi were performed in a similar manner as described previously [8]. Based on the DNA sequencing of ITS of rDNA and the D1/D2 domain of 26S rDNA

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• previously reported methods required high temperatures [118][119][120]. A library of compounds was reported by that group using this approach, and a plausible mechanism is shown in Figure 13. Arylation of purines: Purine bases and purine nucleosides, which are common structural motifs in DNA and RNA, have an

Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo

• Alexander Sailer,
• Franziska Ermer,
• Yvonne Kraus,
• Rebekkah Bingham,
• Ferdinand H. Lutter,
• Julia Ahlfeld and
• Oliver Thorn-Seshold

Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14

• cycle arrest in the G2/M phase by preventing the completion of mitosis [1]. We examined cell cycle repartition by quantification of cellular DNA content via propidium iodide (PI) incorporation, which was analysed by flow cytometry (Supporting Information File 1, Figure S7). HeLa cells were treated for

Reversible photoswitching of the DNA-binding properties of styrylquinolizinium derivatives through photochromic [2 + 2] cycloaddition and cycloreversion

• Sarah Kölsch,
• Heiko Ihmels,
• Jochen Mattay,
• Norbert Sewald and
• Brian O. Patrick

Beilstein J. Org. Chem. 2020, 16, 111–124, doi:10.3762/bjoc.16.13

• -33501 Bielefeld, Germany Department of Chemistry, Structural Chemistry Facility, The University of British Columbia, 2036 Main Mall, V6T 1Z1, Vancouver, BC, Canada 10.3762/bjoc.16.13 Abstract It was demonstrated that styrylquinolizinium derivatives may be applied as photoswitchable DNA ligands. At

• lower ligand:DNA ratios (≤1.5), these compounds bind to duplex DNA by intercalation, with binding constants ranging from Kb = 4.1 × 104 M to 2.6 × 105 M (four examples), as shown by photometric and fluorimetric titrations as well as by CD and LD spectroscopic analyses. Upon irradiation at 450 nm, the

• methoxy-substituted styrylquinolizinium derivatives form the corresponding syn head-to-tail cyclobutanes in a selective [2 + 2] photocycloaddition, as revealed by X-ray diffraction analysis of the reaction products. These photodimers bind to DNA only weakly by outside-edge association, but they release

Photocontrolled DNA minor groove interactions of imidazole/pyrrole polyamides

• Sabrina Müller,
• Jannik Paulus,
• Jochen Mattay,
• Heiko Ihmels,
• Veronica I. Dodero and
• Norbert Sewald

Beilstein J. Org. Chem. 2020, 16, 60–70, doi:10.3762/bjoc.16.8

• compounds have frequently been employed as modules, e.g., to control protein–DNA interactions. However, their use in conjunction with minor groove-binding imidazole/pyrrole (Im/Py) polyamides is yet unprecedented. Dervan-type Im/Py polyamides were equipped with an azobenzene unit, i.e., 3-(3-(aminomethyl

• )phenyl)azophenylacetic acid, as the linker between two Im/Py polyamide strands. Only the (Z)-azobenzene-containing polyamides bound to the minor groove of double-stranded DNA hairpins. Photoisomerization was exemplarily evaluated by 1H NMR experiments, while minor groove binding of the (Z)-azobenzene

• derivatives was proven by CD titration experiments. The resulting induced circular dichroism (ICD) bands of the bound ligands, together with the photometric determination of the dsDNA melting temperature, revealed a significant stabilization of the DNA upon association with the ligand. The (Z)-azobenzene