Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

• Peter Jonas Wickhorst,
• Mathilda Blachnik,
• Denisa Lagumdzija and
• Heiko Ihmels

Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81

• : 6.0 mM Na2HPO4, 2.0 mM NaH2PO4, 1.0 mM Na2EDTA; pH 7.0. All buffer solutions were prepared from purified water (resistivity 18 MΩ cm) and biochemistry-grade chemicals. The buffer solutions were filtered through a PVDF membrane filter (pore size 0.45 μm) prior to use. Structures and numbering of

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• dipalmitoyl-Dap-T7 and dipalmitoyl-Dap-Tat (Figure 1A). Double lipidation ensures a more stable lipid-membrane-anchoring compared to a single fatty acid chain or cholesteryl variant [27][28][29]. The careful choice of Dap and palmitic acid allows for the entire synthesis to be performed on solid support with

• allowed to slowly reach rt, transferred to a 1 mL Hamilton syringe, and extruded 10 times at rt through two 100 nm Nucleopore membrane filters (Whatman) using Avanti Mini Extruder (Avanti Polar Lipids, Inc., USA). Complementary oligonucleotides GP160:A-1 (1.4 nmol, 30 μL 1× PBS pH 7.4) and CCR5:G-3 (1.4

• subsequently incubated overnight at 4 °C with Claudin 5–Alexa Fluor 488 (catalog number 35-258-8, Thermo Fisher Scientific, MA) at 5 µg/mL in 1% BSA–PBS. Thereafter, cells were washed three times with ice-cold PBS. The membrane was subsequently cut out of the insert with a scalpel blade and, using tweezers

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

• ) and for the N+-modified oligos (Figure 3B, H, and K, respectively). Confocal microscope sections that dissect the nucleus were collected showing that the FAM-ON imaged were in the cytoplasm when localised adjacent to the nucleus and not on the cell surface. Staining of the cell membrane, along with

• -ON for 12 hours, then stained with CellBrite Fix 640 (Biotium) to identify the cell membrane before fixation with 4% paraformaldehyde. Nuclear DNA was then stained with Hoechst 3342 and images collected with a Leica SP5 DM6000B scanning confocal microscope. Overlaid pseudo-coloured panels of a

• section are shown: nuclear DNA (blue), 4Ts-FAM/ON (magenta), cell membrane (yellow). Scale bar: 20 μm. The synthesis of ONs with Ts and N+ modification using the Staudinger reaction during the solid-phase DNA synthesis. Conditions: (i) 0.5 M TsN3, MeCN, 37 °C, 30 min for Ts modification; 0.7 M 4

Simulating the enzymes of ganglioside biosynthesis with Glycologue

• Andrew G. McDonald and
• Gavin P. Davey

Beilstein J. Org. Chem. 2021, 17, 739–748, doi:10.3762/bjoc.17.64

• then to subsequent ceramide-linked glycoconjugate acceptors, before transport and eventual incorporation into the plasma membrane via vesicular fusion. Gangliosides, which function as antigenic determinants [4], may play a role in membrane organization [5], cell signaling [6], apoptosis [7], and in

• memory formation through neuromodulation of synaptic transmission [8]. Gangliosides are recycled in the lysosome through the action of glycohydrolases. The inhibition of membrane recycling has been shown to lead to an accumulation of lysosomal gangliosides resulting in neuronal death [9]. Congenital

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

• ]. The modification of oligonucleotides with GuNA[H]-T improved the nuclease resistance, cell membrane permeability, and binding affinity toward complementary single-stranded DNAs (ssDNAs) and RNAs (ssRNAs). We also synthesized and evaluated a GuNA[H]-T analog bearing a methyl group in the guanidine

Synthesis and physicochemical evaluation of fluorinated lipopeptide precursors of ligands for microbubble targeting

• Masayori Hagimori,
• Estefanía E. Mendoza-Ortega and
• Marie Pierre Krafft

Beilstein J. Org. Chem. 2021, 17, 511–518, doi:10.3762/bjoc.17.45

• was stepwisely elongated, and eventually conjugated with the (perfluoroalkyl)ethyl acids (Scheme 2). After the cleavage from the resin, the Fmoc groups of the amino acids were removed, and the F-lipopeptides were purified using a dialysis membrane. According to mass spectrometry, FTIR, and HPLC

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

• study both soluble proteins [26] and membrane proteins [27]. Fluorine tags such at TFET (17) or BFTA (18) offer a good degree of sensitive and narrow 19F NMR line widths due to rapid rotation about the trifluoromethyl symmetry axis. Thus, they are very effective tools when studying small conformational

• further expanded the applications of n-FABS into the screening and direct IC50 measurement of bioactive substrates within intact living cells [45]. By studying mammalian cells expressing the membrane protein fatty acid amide hydrolase (FAAH), they showed that it is possible to screen and identify target

• inhibitors in situ using 19F NMR spectroscopy (Figure 6). For this, the activity of the membrane-bound FAAH enzyme was evaluated by monitoring the hydrolysis of a fluorinated anandamide analogue ARN1203, a previously reported FAAH substrate, to arachidonic acid and 1-amino-3-fluoropropanol in the presence

Multiswitchable photoacid–hydroxyflavylium–polyelectrolyte nano-assemblies

• Alexander Zika and
• Franziska Gröhn

Beilstein J. Org. Chem. 2021, 17, 166–185, doi:10.3762/bjoc.17.17

• (allylamine) with M = 15000 g/mol, the photoacid 1-naphthol-3,6-disulfonate (>90%), and pelargonidin chloride were purchased from Sigma-Aldrich. Deionized water was filtered through two 25 mm syringe filters with a hydrophile membrane consisting of polytetrafluoroethylene with 200 nm pore size. Prior to

Supramolecular polymerization of sulfated dendritic peptide amphiphiles into multivalent L-selectin binders

• David Straßburger,
• Svenja Herziger,
• Katharina Huth,
• Moritz Urschbach,
• Rainer Haag and
• Pol Besenius

Beilstein J. Org. Chem. 2021, 17, 97–104, doi:10.3762/bjoc.17.10

• , these interactions occur in a multivalent fashion, allowing to overcome drawbacks of the limited strength of noncovalent bonds and to tune the selectivity at the same time [1][2]. The binding of viruses to the membrane of their host cells [3][4][5] as well as the recognition of carbohydrates by lectins

Molecular basis for protein–protein interactions

• Brandon Charles Seychell and
• Tobias Beck

Beilstein J. Org. Chem. 2021, 17, 1–10, doi:10.3762/bjoc.17.1

• known as a capsid [78]. Some viruses also have lipid envelopes containing glycoproteins, which interact with the host cell membrane to facilitate the viral entry into the cell [79]. The simplest explanation for viral capsid assembly is protein assembly units colliding (following Brownian motion) in a

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

• ][44]. It is presumed that the antifungal plipastatin, expressed from the ppsA-E gene cluster, acts as an inhibitor of phospholipase A2, forming pores in the fungal membrane and causing morphological changes in the fungal membrane and cell wall [45][46]. This antifungal potential was demonstrated

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

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

• -aminobutyric acid associate with membrane-bound protein receptors and trigger changes in receptor shape and activity with subsequent signaling across the membrane. Noncovalent H-bonding and van der Waals interactions are the basis for the selective molecular recognition between a G-coupled protein receptor and

• membrane-bound receptors interact strongly with short peptidic segments of a larger protein chain, for example, recognition of the RGD sequence (arginine–glycine–aspartic acid; Arg–Gly–Asp) by integrin receptors. They use noncovalent interactions including salt bridges [5]. Vancomycin, a glycopeptide

• chondroitin sulphate. Sensores 10 and 11 even could detect heparin selectively from their mixtures and have been utilized for heparin detection in diluted bovine serum. Lipopolysaccharide detection Endotoxic lipopolysaccharide (LPS) is an important component in the outer cell membrane of Gram-negative

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

• (resistivity ≥ 18 MΩ cm) and filtered through a membrane filter (0.45 µm pore size). K-phosphate-buffer (22AG, a2): 25 mM K2HPO4, 70 mM KCl; pH 7.0; Na-cacodylate buffer (F21T, Fa2T, FmycT, FkitT, and FkrasT): 90 µM LiCl, 10 mM KCl, 10 mM Na(CH3)2AsO2 × 3H2O, pH 7.2–7.3. The K-phosphate buffer solutions and

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

• simpler way to modify the bacterial membrane is by adding to X-ODN-1 a complementary strand (Y-ODN-2) that is modified with the desired functionality (Y) (Figure 1A). In this way, the structure of the artificial receptors can be ‘programmed’ by a simple self-assembly process, which provides the means to

• reversibly change the properties of the cell. For example, we have shown that synthetic receptors appended with a thiol or a folate group enable bacteria expressing the His-tagged outer membrane protein C (His-OmpC) to bind to gold surfaces or cancer cells, respectively [2]. We have also shown that this

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

• structure and properties of the products. The obtained nanoparticles NPrac-1 were purified by using a combination of size exclusion chromatography and membrane filtration. They dispersed freely in water after isolation, giving a stable solution. The 1H NMR spectrum in D2O showed the typical broadened

Comparative ligand structural analytics illustrated on variably glycosylated MUC1 antigen–antibody binding

• Christopher B. Barnett,
• Tharindu Senapathi and
• Kevin J. Naidoo

Beilstein J. Org. Chem. 2020, 16, 2540–2550, doi:10.3762/bjoc.16.206

• secretions and are heavily O-glycosylated [7]. Mucins serve several functions: including protecting the body from pathogens by forming chemical barriers and cellular signaling. Mucin 1 (MUC1) is tethered to the cellular membrane and is found to be aberrantly glycosylated and overexpressed in several

Conformational preferences of fluorine-containing agrochemicals and their implications for lipophilicity prediction

• Daniela Rodrigues Silva,
• Joyce K. Daré and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2020, 16, 2469–2476, doi:10.3762/bjoc.16.200

• on conformation, membrane permeation, pharmacokinetic properties, among other parameters [7]. From a conformational analysis point of view, the fluorine atom presents minimal steric effects; on the other hand, due to its high electronegativity, the C–F bond is highly polarized, which characterizes it

The B & B approach: Ball-milling conjugation of dextran with phenylboronic acid (PBA)-functionalized BODIPY

• Patrizia Andreozzi,
• Lorenza Tamberi,
• Elisamaria Tasca,
• Gina Elena Giacomazzo,
• Marta Martinez,
• Mirko Severi,
• Marco Marradi,
• Stefano Cicchi,
• Sergio Moya,
• Giacomo Biagiotti and
• Barbara Richichi

Beilstein J. Org. Chem. 2020, 16, 2272–2281, doi:10.3762/bjoc.16.188

• 0.044 mmol), 17 mg of PBA-BODIPY (1, 0.044 mmol), and 6.6 mL of dry dimethyl sulfoxide. The mixture was stirred for 6 h, then the product was precipitated in cold ethanol (50 mL), and filtered over a 0.2 µm nylon membrane. The powder was recovered and dispersed (6.8 mg/mL) in ethanol and sonicated for 5

• min at 59 kHz. The dispersion was filtered over a 0.2 µm nylon membrane recovering both solid and solution. This protocol was repeated and then the solid was washed over the filter with ethanol (2 × 30 mL) and dried under vacuum to obtain 250 mg of Dex-1a as orange solid. FTIR data are shown in Figure

• was recovered, dissolved in DMSO (6.6 mL) and the product precipitated from cold ethanol (50 mL) and filtered over a 0.2 µm nylon membrane. The powder was recovered and dispersed (6.8 mg/mL) in ethanol and sonicated for 5 min at 59 kHz. The dispersion was filtered over a 0.2 µm nylon membrane

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• liability for phospholipidosis [20], iii) an increased membrane permeability [21] and iv) the mitigation of undesired binding to the human ether a-go-go-related gene (hERG) K+ channel associated with cardiovascular toxicity [22]. Moreover, the radiochemical properties of the 18F nucleus render them crucial

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

• challenge is most pronounced with large substrates, such as proteins, oligonucleotides, or nanoparticles, due to the permeability barriers formed by the lipophilic core of the cell membrane [18][19]. In recent decades, the use of arginine-rich cell-penetrating peptides (CPPs) as carriers has emerged as an

• attractive approach to tackle this central challenge [1][2][3][11][12][13][14]. The noncovalent interaction between the guanidinium cations from CPPs and cell membrane-associated anions, such as phospholipids, proteoglycans, or sialic acids, is considered to enhance the cell surface accumulation of

• added to minimize the passive diffusion across the membrane and to maximize the solubility in water. Biotin was used to interface the transporter and streptavidin to probe the COC-mediated protein delivery. A chloroalkane, finally, was needed for the HC CAPA. The trifunctional transporter 23 was first

Design, synthesis and application of carbazole macrocycles in anion sensors

• Alo Rüütel,
• Ville Yrjänä,
• Sandip A. Kadam,
• Indrek Saar,
• Mihkel Ilisson,
• Astrid Darnell,
• Kristjan Haav,
• Tõiv Haljasorg,
• Lauri Toom,
• Johan Bobacka and
• Ivo Leito

Beilstein J. Org. Chem. 2020, 16, 1901–1914, doi:10.3762/bjoc.16.157

• this protein-inspired architecture have recently been praised in the use of naphthotubes [3]. Association between the receptor and the analyte may change considerably when the receptor is attached to an electrode surface or embedded in a sensor membrane. Water, as the most common environment for real

• -life sensing, also influences binding [4]. Within an ion-selective electrode (ISE), lipophilicity is mostly contributed by the low polarity membrane, which is commonly based on plasticized PVC [5]. One possible receptor family for carboxylates is based on the biscarbazolylurea moiety (Figure 1). This

• functional groups in the 3,6-positions of the carbazole. High lipophilicity is achievable by using alkylation and leads to the possibility of using the receptor dissolved in the lipophilic polymeric sensor membrane, without the need for chemical linking. Cyclization of the receptor is possible via the

On the hydrolysis of diethyl 2-(perfluorophenyl)malonate

• Ilya V. Taydakov and
• Mikhail A. Kiskin

Beilstein J. Org. Chem. 2020, 16, 1863–1868, doi:10.3762/bjoc.16.153

• to be one of the most powerful tools for fine tuning of chemical and physical properties [19][20]. For example, thermal stability, solubility, metabolic and oxidative stability, lipophilicity, membrane permeability, complexing ability, acid-base, and many other properties can be modified in a broad

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

• Bern, Switzerland Department of Biochemistry, Weill Cornell Medical College, 1300 York Avenue, 10065 New York, United States of America 10.3762/bjoc.16.145 Abstract The chemical synthesis of molecular probes to identify and study membrane proteins involved in the biological pathway of protein

• ) [1][2][3][4][5][6][7][8]. Interestingly, MPD is synthesized on the cytoplasmic face of the ER and must be translocated across the ER membrane to participate in luminal glycosyltransfer reactions [3][4]. A specific membrane protein – MPD scramblase – is required to facilitate the transbilayer movement

• membrane proteins [11][12]. The captured proteins would be subsequently identified by mass spectrometry, and their function in MPD scrambling validated by biochemical and genetic approaches. A suitable molecular probe and mimic of MPD (Figure 1) can be subdivided into three essential components: a β-ᴅ

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

Disposable cartridge concept for the on-demand synthesis of turbo Grignards, Knochel–Hauser amides, and magnesium alkoxides

• Mateo Berton,
• Kevin Sheehan,
• Andrea Adamo and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2020, 16, 1343–1356, doi:10.3762/bjoc.16.115

• ) Inside view of the pump with a flexible bag containing a yellow liquid laying on an elastomer membrane. B) Detail of the manifold used to select the waste or product collection. C) Heater cross section, the arrows indicate the air convection flow path. D) Reagents on-demand system assembled, with the