TY - JOUR A1 - Abdelhameed, Reda F. A. A1 - Eltamany, Enas E. A1 - Hal, Dina M. A1 - Ibrahim, Amany K. A1 - AboulMagd, Asmaa M. A1 - Al-Warhi, Tarfah A1 - Youssif, Khayrya A. A1 - Abd El-kader, Adel M. A1 - Hassanean, Hashim A. A1 - Fayez, Shaimaa A1 - Bringmann, Gerhard A1 - Ahmed, Safwat A. A1 - Abdelmohsen, Usama Ramadan T1 - New cytotoxic cerebrosides from the Red Sea cucumber Holothuria spinifera supported by in-silico studies JF - Marine Drugs N2 - Bioactivity-guided fractionation of a methanolic extract of the Red Sea cucumber Holothuria spinifera and LC-HRESIMS-assisted dereplication resulted in the isolation of four compounds, three new cerebrosides, spiniferosides A (1), B (2), and C (3), and cholesterol sulfate (4). The chemical structures of the isolated compounds were established on the basis of their 1D NMR and HRMS spectral data. Metabolic profiling of the H. spinifera extract indicated the presence of diverse secondary metabolites, mostly hydroxy fatty acids, diterpenes, triterpenes, and cerebrosides. The isolated compounds were tested for their in vitro cytotoxicities against the breast adenocarcinoma MCF-7 cell line. Compounds 1, 2, 3, and 4 displayed promising cytotoxic activities against MCF-7 cells, with IC\(_{50}\) values of 13.83, 8.13, 8.27, and 35.56 µM, respectively, compared to that of the standard drug doxorubicin (IC\(_{50}\) 8.64 µM). Additionally, docking studies were performed for compounds 1, 2, 3, and 4 to elucidate their binding interactions with the active site of the SET protein, an inhibitor of protein phosphatase 2A (PP2A), which could explain their cytotoxic activity. This study highlights the important role of these metabolites in the defense mechanism of the sea cucumber against fouling organisms and the potential uses of these active molecules in the design of new anticancer agents. KW - LC-HRESIMS KW - Holothuria spinifera KW - cerebrosides KW - molecular docking KW - cytotoxicity Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-211089 SN - 1660-3397 VL - 18 IS - 8 ER - TY - JOUR A1 - Steinmetzger, Christian A1 - Bessi, Irene A1 - Lenz, Ann-Kathrin A1 - Höbartner, Claudia T1 - Structure-fluorescence activation relationships of a large Stokes shift fluorogenic RNA aptamer JF - Nucleic Acids Research N2 - The Chili RNA aptamer is a 52 nt long fluorogen-activating RNA aptamer (FLAP) that confers fluorescence to structurally diverse derivatives of fluorescent protein chromophores. A key feature of Chili is the formation of highly stable complexes with different ligands, which exhibit bright, highly Stokes-shifted fluorescence emission. In this work, we have analyzed the interactions between the Chili RNA and a family of conditionally fluorescent ligands using a variety of spectroscopic, calorimetric and biochemical techniques to reveal key structure - fluorescence activation relationships (SFARs). The ligands under investigation form two categories with emission maxima of ~540 nm or ~590 nm, respectively, and bind with affinities in the nanomolar to low-micromolar range. Isothermal titration calorimetry was used to elucidate the enthalpic and entropic contributions to binding affinity for a cationic ligand that is unique to the Chili aptamer. In addition to fluorescence activation, ligand binding was also observed by NMR spectroscopy, revealing characteristic signals for the formation of a G-quadruplex only upon ligand binding. These data shed light on the molecular features required and responsible for the large Stokes shift and the strong fluorescence enhancement of red and green emitting RNA-chromophore complexes. KW - Chili RNA Aptamer KW - fluorogen-activating RNA aptamer (FLAP) KW - Stokes-shifted fluorescence emission KW - key structure - fluorescence activation relationships (SFARs) KW - ligand binding Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-192340 ER - TY - JOUR A1 - Suliman, Salwa A1 - Mustafa, Kamal A1 - Krueger, Anke A1 - Steinmüller-Nethl, Doris A1 - Finne-Wistrand, Anna A1 - Osdal, Tereza A1 - Hamza, Amani O. A1 - Sun, Yang A1 - Parajuli, Himalaya A1 - Waag, Thilo A1 - Nickel, Joachim A1 - Johannessen, Anne Christine A1 - McCormack, Emmet A1 - Costea, Daniela Elena T1 - Nanodiamond modified copolymer scaffolds affects tumour progression of early neoplastic oral keratinocytes JF - Biomaterials N2 - This study aimed to evaluate the tumorigenic potential of functionalising poly(LLA-co-CL) scaffolds. The copolymer scaffolds were functionalised with nanodiamonds (nDP) or with nDP and physisorbed BMP-2 (nDP-PHY) to enhance osteoinductivity. Culturing early neoplastic dysplastic keratinocytes (DOK\(^{Luc}\)) on nDP modified scaffolds reduced significantly their subsequent sphere formation ability and decreased significantly the cells' proliferation in the supra-basal layers of in vitro 3D oral neoplastic mucosa (3D-OT) when compared to DOK\(^{Luc}\) previously cultured on nDP-PHY scaffolds. Using an in vivo non-invasive environmentally-induced oral carcinogenesis model, nDP scaffolds were observed to reduce bioluminescence intensity of tumours formed by DOK\(^{Luc}\) + carcinoma associated fibroblasts (CAF). nDP modification was also found to promote differentiation of DOK\(^{Luc}\) both in vitro in 3D-OT and in vivo in xenografts formed by DOKLuc alone. The nDP-PHY scaffold had the highest number of invasive tumours formed by DOK\(^{Luc}\) + CAF outside the scaffold area compared to the nDP and control scaffolds. In conclusion, in vitro and in vivo results presented here demonstrate that nDP modified copolymer scaffolds are able to decrease the tumorigenic potential of DOK\(^{Luc}\), while confirming concerns for the therapeutic use of BMP-2 for reconstruction of bone defects in oral cancer patients due to its tumour promoting capabilities. KW - Bone morphogenetic protein-2 KW - Sinus floor augmentation KW - Marrow stromal cells KW - Growth; BMP-2 KW - Tumorigenicity KW - Biodegradable polymer scaffolds KW - Mandibular continuity defects KW - Squamous-cell carcinoma KW - In-vitro KW - Mesenchymal transition KW - BMP-2 KW - Bone tissue engineering KW - Biocompatibility KW - Microenvironment KW - Oral squamous cell carcinoma Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188287 VL - 95 ER - TY - JOUR A1 - Scheitl, Carolin P. M. A1 - Lange, Sandra A1 - Höbartner, Claudia T1 - New deoxyribozymes for the native ligation of RNA JF - Molecules N2 - Deoxyribozymes (DNAzymes) are small, synthetic, single-stranded DNAs capable of catalysing chemical reactions, including RNA ligation. Herein, we report a novel class of RNA ligase deoxyribozymes that utilize 5’-adenylated RNA (5’-AppRNA) as the donor substrate, mimicking the activated intermediates of protein-catalyzed RNA ligation. Four new DNAzymes were identified by in vitro selection from an N40 random DNA library and were shown to catalyze the intermolecular linear RNA-RNA ligation via the formation of a native 3’-5’-phosphodiester linkage. The catalytic activity is distinct from previously described RNA-ligating deoxyribozymes. Kinetic analyses revealed the optimal incubation conditions for high ligation yields and demonstrated a broad RNA substrate scope. Together with the smooth synthetic accessibility of 5’-adenylated RNAs, the new DNA enzymes are promising tools for the protein-free synthesis of long RNAs, for example containing precious modified nucleotides or fluorescent labels for biochemical and biophysical investigations. KW - RNA ligation KW - DNA catalysis KW - in vitro selection KW - Deoxyribozyme Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-210405 VL - 25 IS - 16 ER - TY - JOUR A1 - Renner, Rebecca A1 - Stolte, Matthias A1 - Würthner, Frank T1 - Self-Assembly of bowl-shaped naphthalimide-annulated corannulene JF - ChemistryOpen N2 - The self-assembly of a bowl-shaped naphthalimide-annulated corannulene of high solubility has been studied in a variety of solvents by NMR and UV/Vis spectroscopy. Evaluation by the anti-cooperative K\(_2\)-K model revealed the formation of supramolecular dimers of outstanding thermodynamic stability. Further structural proof for the almost exclusive formation of dimers over extended aggregates is demonstrated by atomic force microscopy (AFM) and diffusion ordered spectroscopy (DOSY) measurements as well as by theoretical calculations. Thus, herein we present the first report of a supramolecular dimer of an annulated corannulene derivative in solution and discuss its extraordinarily high thermodynamic stability with association constants up to > 10\(^6\)M\(^-\) \(^1\) in methylcyclohexane, which is comparable to the association constants given for planar phthalocyanine and perylene bisimide dyes. KW - corannulene KW - π-π-interactions KW - aelf-assembly KW - aggregation KW - supramolecular chemistry Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204396 VL - 9 IS - 1 ER - TY - JOUR A1 - Pöppler, Ann-Christin A1 - Lübtow, Michael M. A1 - Schlauersbach, Jonas A1 - Wiest, Johannes A1 - Meinel, Lorenz A1 - Luxenhofer, Robert T1 - Loading dependent Structural Model of Polymeric Micelles Encapsulating Curcumin by Solid-State NMR Spectroscopy JF - Angewandte Chemie International Edition N2 - Detailed insight into the internal structure of drug‐loaded polymeric micelles is scarce, but important for developing optimized delivery systems. We observed that an increase in the curcumin loading of triblock copolymers based on poly(2‐oxazolines) and poly(2‐oxazines) results in poorer dissolution properties. Using solid‐state NMR spectroscopy and complementary tools we propose a loading‐dependent structural model on the molecular level that provides an explanation for these pronounced differences. Changes in the chemical shifts and cross‐peaks in 2D NMR experiments give evidence for the involvement of the hydrophobic polymer block in the curcumin coordination at low loadings, while at higher loadings an increase in the interaction with the hydrophilic polymer blocks is observed. The involvement of the hydrophilic compartment may be critical for ultrahigh‐loaded polymer micelles and can help to rationalize specific polymer modifications to improve the performance of similar drug delivery systems. KW - dissolution rates KW - micelles KW - polymers KW - short-range order KW - solid-state NMR spectroscopy Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-206705 VL - 58 IS - 51 ER - TY - JOUR A1 - Zhang, Fangyuan A1 - Michail, Evripidis A1 - Saal, Fridolin A1 - Krause, Ana-Maria A1 - Ravat, Prince T1 - Stereospecific Synthesis and Photophysical Properties of Propeller-Shaped C\(_{90}\)H\(_{48}\) PAH JF - Chemistry - A European Journal N2 - Herein, we have synthesized an enantiomerically pure propeller‐shaped PAH, C\(_{90}\)H\(_{48}\), possessing three [7]helicene and three [5]helicene subunits. This compound can be obtained in gram quantities in a straightforward manner. The photophysical and chiroptical properties were investigated using UV/Vis absorption and emission, optical rotation and circular dichroism spectroscopy, supported by DFT calculations. The nonlinear optical properties were investigated by two‐photon absorption measurements using linearly and circularly polarized light. The extremely twisted structure and packing of the homochiral compound were investigated by single‐crystal X‐ray diffraction analysis. KW - chirality KW - enantiomers KW - helicenes KW - polycyclic aromatic hydrocarbons KW - stereospecific sythesis Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-208682 VL - 25 IS - 71 ER - TY - JOUR A1 - Seifert, Sabine A1 - Shoyama, Kazutaka A1 - Schmidt, David A1 - Würthner, Frank T1 - An electron-poor C\(_{64}\) nanographene by palladium-catalyzed cascade C-C bond formation: one-pot synthesis and single-crystal structure analysis JF - Angewandte Chemie-International Edition N2 - Herein, we report the one-pot synthesis of an electron-poor nanographene containing dicarboximide groups at the corners. We efficiently combined palladium-catalyzed Suzuki-Miyaura cross-coupling and dehydrohalogenation to synthesize an extended two-dimensional pi-scaffold of defined size in a single chemical operation starting from N-(2,6-diisopropylphenyl)-4,5-dibromo-1,8-naphthalimide and a tetrasubstituted pyrene boronic acid ester as readily accessible starting materials. The reaction of these precursors under the conditions commonly used for Suzuki-Miyaura cross-coupling afforded a C\(_{64}\) nanographene through the formation of ten C-C bonds in a one-pot process. Single-crystal X-ray analysis unequivocally confirmed the structure of this unique extended aromatic molecule with a planar geometry. The optical and electrochemical properties of this largest ever synthesized planar electron-poor nanographene skeleton were also analyzed. KW - Graphene nanoribbons KW - Liquid-crystalline KW - dyes/pigments KW - polycyclic aromatic hydrocarbons KW - two-dimensional nanostructures KW - Aromatic-hydrocarbon KW - Carbon KW - Dyes KW - Functionalization KW - cascade reactions KW - nanographene Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188889 VL - 55 IS - 22 ER - TY - JOUR A1 - Maghami, Mohammad Ghaem A1 - Dey, Surjendu A1 - Lenz, Ann-Kathrin A1 - Höbartner, Claudia T1 - Repurpsing Antiviral Drugs for Orthogonal RNA-Catalyzed Labeling JF - Angewandte Chemie, International Edition N2 - In vitro selected ribozymes are promising tools for site-specific labeling of RNA. Previously known nucleic acid catalysts attached fluorescently labeled adenosine or guanosine derivatives through 2’,5’-branched phosphodiester bonds to the RNA of interest. Herein, we report new ribozymes that use orthogonal substrates, derived from the antiviral drug tenofovir, and attach bioorthogonal functional groups, as well as affinity handles and fluorescent reporter units through a hydrolytically more stable phosphonate ester linkage. The tenofovir transferase ribozymes were identified by in vitro selection and are orthogonal to nucleotide transferase ribozymes. As genetically encodable functional RNAs, these ribozymes may be developed for potential cellular applications. The orthogonal ribozymes addressed desired target sites in large RNAs in vitro, as shown by fluorescent labeling of E. coli 16S and 23S RNAs in total cellular RNA. KW - Antiviral nucleoside analogues KW - in vitro selection KW - ribozymes KW - site-specific RNA labeling KW - tenofovir Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-205552 VL - 59 ER - TY - JOUR A1 - Renner, Rebecca A1 - Mahlmeister, Bernhard A1 - Anhalt, Olga A1 - Stolte, Matthias A1 - Würthner, Frank T1 - Chiral Perylene Bisimide Dyes by Interlocked Arene Substituents in the Bay Area JF - Chemistry - A European Journal N2 - A series of perylene bisimide (PBI) dyes bearing various aryl substituents in 1,6,7,12 bay positions has been synthesized by Suzuki cross-coupling reaction. These molecules exhibit an exceptionally large and conformationally fixed twist angle of the PBI π-core due to the high steric congestion imparted by the aryl substituents in bay positions. Single crystal X-ray analyses of phenyl-, naphthyl- and pyrenyl-functionalized PBIs reveal interlocked π-π-stacking motifs, leading to conformational chirality and the possibility for the isolation of enantiopure atropoisomers by semipreparative HPLC. The interlocked arrangement endows these molecules with substantial racemization barriers of about 120 kJ mol\(^{−1}\) for the tetraphenyl- and tetra-2-naphthyl-substituted derivatives, which is among the highest racemization barriers for axially chiral PBIs. Variable temperature NMR studies reveal the presence of a multitude of up to fourteen conformational isomers in solution that are interconverted via smaller activation barriers of about 65 kJ mol\(^{−1}\). The redox and optical properties of these core-twisted PBIs have been characterized by cyclic voltammetry, UV/Vis/NIR and fluorescence spectroscopy and their respective atropo-enantiomers were further characterized by circular dichroism (CD) and circular polarized luminescence (CPL) spectroscopy. KW - Suzuki coupling KW - perylenebisimide dyes KW - circular polarized luminescence KW - chirality Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-249070 VL - 27 IS - 46 SP - 11997 EP - 12006 ER -