Solution structure of a purine rich hexaloop hairpin belonging to PGY/MDR1 mRNA and targeted by antisense oligonucleotides

A preferential target of antisense oligonucleotides directed against human PGY/MDR1 mRNA is a hairpin containing a stem with a G•U wobble pair, capped by the purine-rich (5′)r(GGGAUG)(3′) hexaloop. This hairpin is studied by multidimensional NMR and restrained molecular dynamics, with special emphasis on the conformation of south sugars and non-standard phosphate linkages evidenced in both the stem and the loop. The hairpin is found to be highly structured. The G•U wobble pair, a strong counterion binding site, displays structural particularities that are characteristic of this type of mismatch. The upper part of the stem undergoes distortions that optimize its interactions with the beginning of the loop. The loop adopts a new fold in which the single-stranded GGGA purine tract is structured in A-like conformation stacked in continuity of the stem and displays an extensive hydrogen bonding surface for recognition. The remarkable hairpin stability results from classical inter- and intra-strand interactions reinforced by numerous hydrogen bonds involving unusual backbone conformations and ribose 2′-hydroxyl groups. Overall, this work emphasizes numerous features that account for the well-ordered structure of the whole hairpin and highlights the loop properties that facilitate interaction with antisense oligonucleotides

Synthesis and inclusion ability of anthracene appended beta-cyclodextrins: unexpected effect of triazole linker

1 - ArticleA new fluorescent beta-cyclodextrin has been synthesized by coupling an anthracene moiety to the cyclic oligosaccharide via click chemistry. The influence of the triazole spacer was compared to the simple amino and amido linkers. While a sensing ability toward adamantan-1-ol was observed with the latter two spacers, the absence of inclusion capacity prevents the triazole modified cyclodextrin from showing any fluorescence variations. The difference in the binding behaviors studied by Isothermal Titration Calorimetry, UV-vis and fluorescence spectroscopies, was highlighted by the NOESY NMR spectra of the modified cyclodextrins: whereas a free cavity was observed for the amino and amido linkers, an important obstruction was obtained in the case of the triazole. (C) 2010 Elsevier Ltd. All rights reserved

Propriétés structurales de la craboline, un peptide antimicrobien naturel

International audienceA joint application of experimental and computational approaches has revealed the exceptionally high attitude of crabrolin, a 13-residue peptide with sequence FLPLILRKIVTAL-NH2, to adopt alpha-helix conformation not only in membrane-mimicking solvents but also in the presence of a not negligible amount of water. Our study shows that this propensity essentially resides in the intrinsic thermodynamic stability of alpha-helix conformation whose kinetic stability is drastically reduced in water solvent. Our analysis suggest that this is due to two effects enhanced by water; a more local effect consisting of the demolition of intra-peptide H-bonds, essential for the alpha-helix formation, and a bulk-electrostatic-effect favoring conformational states more polar than alpha-helix

Flavin-adenine-dinucleotide gold complex nanoparticles: chemical modeling design, physico-chemical assessment and perspectives in nanomedicine

International audienceFlavoproteins play an important role in the regulatory process of cell life, and they are involved in several redox reactions that regulate the metabolism of carbohydrates, amino acids, and lipids. The development of effective drug delivery systems is one of the major challenges in the fight against cancer. This study involves a nanomedicine pathway to encapsulate the cofactor flavin adenine dinucleotide (FAD) using polymeric gold nanoparticles (PEG-AuNPs) through two chemical methods of functionalization (chelation (IN); carbodiimide chemistry (ON)). These hybrid gold nanoparticles and their precursors were characterized by analytical techniques (Raman, UV-Vis, and H 1-NMR spectroscopy and transmission electron microscopy (TEM)) which confirmed the grafting of the cofactor agent. The results of the computational studies (Density Functional Theory (DFT)) were in agreement with the experimental observations. We also monitored the interaction of our hybrid nanoparticle systems with small aptamers (APT) in order to validate the hypotheses on the biomolecular mechanisms and also investigate their biological efficiency on pancreatic cancer cells (MIAPaCa-2 cells)

Correction: Flavin-adenine-dinucleotide gold complex nanoparticles: chemical modeling design, physico-chemical assessment and perspectives in nanomedicine

Correction for 'Flavin-adenine-dinucleotide gold complex nanoparticles: chemical modeling design, physico-chemical assessment and perspectives in nanomedicine' by Celia Arib et al., Nanoscale Adv., 2021, 3, 6144-6156, https://doi.org/10.1039/D1NA00444A

Idarubicin–Gold Complex: From Crystal Growth to Gold Nanoparticles

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Pigments photosynthétiques, enzymes antioxydantes et potentiel osmotique foliaire de dix génotypes de blé dur (Triticum durum) : effet du stress hydrique

L’ajustement osmotique, les pigments photosynthétiques et les changements d’activités des antioxydants enzymatiques ont été évalués chez dix génotypes de blé dur (Triticum durum) soumis à des conditions de stress hydrique. Les plantules de blé ont germé en hydroponie, en chambre de culture. Le stress hydrique a été appliqué aux quatrième et cinquième stades de la feuille par l’ajout d’une solution de polyéthylène glycol (PEG 6000) (-0,49 MPa). Le potentiel osmotique ainsi que la teneur en chlorophylle totale (Chl a+b) et en caroténoïdes (Car) ont été déterminés. Des analyses électrophorétiques ont été effectuées pour trois enzymes antioxydantes, soit la superoxyde dismutase (SOD), la guaïacol peroxydase (GPOX) et la catalase (CAT), en utilisant l’électrophorèse sur gel de polyacrylamide (PAGE) en conditions natives. Les résultats obtenus montrent une réduction du potentiel osmotique foliaire et une diminution de Chl a+b et Car sous l’effet du stress hydrique. Toutefois, il existe des différences significatives entre les génotypes étudiés en réponse au traitement imposé. PAGE a permis de montrer une augmentation dans l’intensité des enzymes étudiées et une apparition d’isoformes supplémentaires, dont une de CAT et trois de SOD, en conditions de stress. Ces différences dans les réponses au stress hydrique pourraient être des indices utiles et fiables pour la sélection de génotypes tolérants de blé dur.Osmotic adjustment, photosynthetic pigments and changes in antioxidant enzyme activities were evaluated in ten durum wheat (Triticum durum) genotypes under water stress conditions. The wheat seedlings germinated in hydroponic conditions in a growth chamber. Water deficit was performed at the fourth and fifth leaf stages using a polyethylene glycol (PEG 6000) solution (-0.49 MPa). Osmotic potential as well as total chlorophyll (Chl a+b) and carotenoid (Car) contents were investigated. Electrophoretic analyses were performed for three antioxidant enzymes: superoxide dismutase (SOD), guaiacol peroxidase (GPOX) and catalase (CAT) using native polyacrylamide gel electrophoresis (PAGE). The results obtained show a reduction in leaf osmotic potential and a decrease in Chl a+b and Car contents under water stress conditions. However, there are significant differences between the genotypes studied in their response to the treatment. PAGE showed an increased intensity in the enzymes studied and the appearance of additional isoforms, including one CAT and three SOD, under stress conditions. These differences in water stress response could be useful and reliable indices for the selection of tolerant durum wheat genotypes