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Reactions between the antibacterial fluoroquinolone agent ciprofloxacin (CIP) and organic hydrophilic nanoflakes (graphene oxide and boron nitride oxide) have been studied in aqueous medium using density functional theory (DFT), time-dependent density functional theory (TD-DFT), and molecular dynamics (MD) simulations. We found that CIP molecules in π-π electron donor-acceptor (EDA) reaction preserve their optical properties in water when adsorbed on hydrophilic nanoflakes. Moreover, MD calculations aimed at studying the diffusive translocation of CIP to lipid membrane showed that the choice of the hydrophilic nanovectors is primordial to stabilize the molecule on the cellular membrane and improve cytotoxic effects.

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The behavior of confined anticancer carboplatin (CPT) molecules in a single (10, 10) boron nitride nanotube (BNNT) was studied by means of molecular dynamics simulations. Our study revealed a very large storage capacity of BNNT. Analysis of the energy profiles depending on the number of confined molecules, and on their spatial organization allowed us to quantify the ability of BNNT to vectorize CPT. Indeed, BNNT despite its small radius presented a large inner volume that favored stable encapsulation of multiple active anticancer molecules. Moreover, in our molecular dynamics simulations, the empty BNNT and the BNNT filled with CPT diffused spontaneously to the cell membrane and were able to passively enter inside lipid bilayers by a lipid-assisted mechanism. This property has been used to deliver naturally anticancer drugs to cellular targets. Using this enhanced drug delivery system, we have provided a definitive solution to the problem of drug release and have thus opened up a new way of targeting cancer cells. Indeed, regardless of the mode of action of the platinum complex towards the cell, the delivery of the drug on site should limit the side effects of the drug.

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Density functional theory calculations with van der Waals approximation have been conducted to analyze the functionalization of various carbon-based nanostructures (fullerene, metallic, and semi-conducting nanotubes) with amino derivative groups. The results obtained with azomethine, show the formation of a five membered ring on fullerenes, and on nanotubes consistent with experimental observations. The attachment of an azomethine plus subsequent drug like a Pt(IV) complex does not perturb the cycloaddition process. Moreover, all theoretical results show that the length of different amino derivatives with subsequent Pt(IV) complex does not affect the complexed therapeutic agent when it is attached onto these carbon-based nanostructures.

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Organic nanostructures on semiconductors are currently investigated but the surfaces are known to interact strongly with molecules. To reduce the molecule-surface interaction, we used the Si(111)-B square root 3 x square root 3R30 degrees . Deposition of isolated 2,4,6-tri(2'-thienyl)-1,3,5-triazine, was achieved at room temperature without modification of their pi skeleton. This fascinating arrangement, observed by STM, has been validated by full density functional theory computations onto the entire system. The theoretical results give a clear explanation for the specific adsorption sites of molecules on the substrate.

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Neoglycoconjugates are useful tools to study carbohydrate/protein interactions. In order to discover new lectins, to define their fine specificity or to study their intracellular trafficking, there is a need for neoglycoconjugates containing complex oligosaccharides. We recently set up a simple way to transform native oligosaccharides into glycosynthons. The present paper describes i) the synthesis of such glycosynthons starting with sialylated oligosides, ii) the preparation of sialylated neoglycoproteins and iii) their binding to sialic acid-specific lectins assessed by surface plasmon resonance experiments.

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Nuclear proteins bearing O-linked N-acetylglucosaminyl residues are involved in nuclear transport and in transcriptional processes. However, the role of glycosylation remains to be determined. It was proposed that glycosylation could be involved in macromolecular complex formation or in nuclear targeting. In the present study, we show that, in digitonin-permeabilized cells, BSA substituted with beta-di-N-acetylchitobioside (GlcNAc beta 4GlcNAc) is transported from the cytosol to the nucleus in a sugar dependent manner. The process is time and ATP dependent. Under the conditions used, the nuclear import of beta-di-N-acetyl-chitobios BSA, as it has also been previously shown for the nuclear import of alpha-glucosyl BSA (Duverger et al., J. Cell Sci., 108, 1325-1332, 1995) does not require the addition of a cytosolic extract, while the nuclear import of peptidic-NLS substituted BSA does require such an addition. These results suggest that GlcNAc can act as a nuclear localization signal.

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The nuclear import of many proteins depends on a short peptide sequence called the nuclear localization signal. However, glycosylated proteins, which lack such a nuclear localization signal, upon their injection into the cytosol by electroporation, enter the nucleus in a sugar-dependent manner. This paper brings new insights on the mechanism of this process, based on a study of neoglycoprotein nuclear uptake by digitonin-permeabilized cells. The nuclear import of neoglycoproteins is energy dependent: it does not occur when cells are maintained at 4 degrees C or when cells are ATP-depleted by treatment with apyrase. The nuclear import of neoglycoproteins occurs through the nuclear pore: it is inhibited by preincubation of cells with wheat germ agglutinin, a lectin which binds the nuclear pore glycoproteins and blocks the translocation step of nuclear localization signal bearing proteins through the nuclear pore. Furthermore, the nuclear import of neoglycoproteins does not use the pathway of nuclear localization signal bearing proteins: nuclear import of nuclear localization signal bearing proteins depends on cytosolic factors and is inhibited by treatment of cells with N-ethylmaleimide, while the nuclear import of neoglycoproteins neither requires added cytosolic factors nor is sensitive to alkylation by N-ethylmaleimide. In addition, upon incubation in the presence of a large excess of nuclear localization signal bearing protein, the nuclear import of neoglycoproteins is not inhibited.

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Large proteins (above 40 kDa) do not migrate from the cytosol to the nucleus except when they contain or are substituted with specific peptides called nuclear localization sequence. Accordingly fluorescein-labeled serum albumin, introduced into the cytosol upon electroporation, does not leave the cytosol. Conversely the same protein substituted with about 25 sugar residues migrate from the cytosol to the nucleus in a manner dependent on the nature of the sugar linked to serum albumin, on the temperature, and on the incubation time. Serum albumin substituted with glucose, fucose, or mannose residues enter the nucleus at 37 degrees C within 30 min while sugar-free serum albumin or serum albumin substituted with galactoside or 6-phosphomannoside residues do not. At 4 degrees C, all of those proteins stay in the cytosol. Thus, glycosylated proteins can enter the nucleus from the cytosol by making use of the sugars borne either by a new type of nuclear import or by making a complex with lectins acting as shuttle between cytosol and nucleus.

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