24 research outputs found

    Free-Space Quantum Signatures Using Heterodyne Measurements

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    Digital signatures guarantee the authorship of electronic communications. Currently used "classical" signature schemes rely on unproven computational assumptions for security, while quantum signatures rely only on the laws of quantum mechanics. Previous quantum signature schemes have used unambiguous quantum measurements. Such measurements, however, sometimes give no result, reducing the efficiency of the protocol. Here, we instead use heterodyne detection, which always gives a result, although there is always some uncertainty. We experimentally demonstrate feasibility in a real environment by distributing signature states through a noisy 1.6km free-space channel. Our results show that continuous-variable heterodyne detection improves the signature rate for this type of scheme and therefore represents an interesting direction in the search for practical quantum signature schemes

    Synthesis, enzymatic stability and in vitro cytostatic effect of Daunorubicin-GnRH-III derivative dimers

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    Bioconjugates containing chemotherapeutic agents attached to peptide hormones, such as gonadotropin-releasing hormone (GnRH), are developed as drug delivery systems for targeted cancer chemotherapy. We report here the synthesis and biochemical characterization of disulfide bond-linked dimeric biocon-jugates in which daunorubicin was coupled via an oxime linkage to aminooxyacetylated GnRH-III ([Glp-His-Trp-Ser-His-Asp-Trp-Lys(Dau@Aoa-Cys)-Pro-Gly-NH2]2; where Glp is pyroglutamic acid and Aoa is aminooxyacetyl) and its derivatives modified in position four byN-Me-Ser and Lys(Ac). The in vitro sta-bility/degradation of the bioconjugates was determined in human serum, as well as in the presence of rat liver lysosomal homogenate and digestive enzymes. All compounds were stable at least for 24 h in human serum and in the presence of pepsin and trypsin, while they were degraded by lysosomal enzymes. The daunorubicin-GnRH-III derivative dimers were partly digested bya-chymotrypsin; how-ever, they had increased stability compared to the corresponding monomers, making them potential can-didates for oral administration. The in vitro cytostatic effect of the compounds was determined on MCF-7 human breast cancer cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. All daunorubicin-GnRH-III derivative dimers exerted slightly increased in vitro cytostatic effect (IC50values in low lM range) than the corresponding monomeric bioconjugates

    Mass spectrometric approaches for elucidation of antigen antibody recognition structures in molecular immunology

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    Mass spectrometric approaches have recently gained increasing access to molecular immunology and several methods have been developed that enable detailed chemical structure identification of antigen-antibody interactions. Selective proteolytic digestion and MS-peptide mapping (epitope excision) has been successfully employed for epitope identification of protein antigens. In addition, affinity proteomics using partial epitope excision has been developed as an approach with unprecedented selectivity for direct protein identification from biological material. The potential of these methods is illustrated by the elucidation of a β- amyloid plaque-specific epitope recognized by therapeutic antibodies from transgenic mouse models of Alzheimer s disease. Using an immobilized antigen and antibody- proteolytic digestion and analysis by high resolution Fourier transform ion cyclotron resonance mass spectrometry has lead to a new approach for the identification of antibody paratope structures (paratope-excision; parexprot ). In this method, high resolution MS-peptide data at the low ppm level are required for direct identification of paratopes using protein databases. Mass spectrometric epitope mapping and determination of molecular antibody-recognition signatures offer high potential, especially for the development of new molecular diagnostics and the evaluation of new vaccine lead structures

    Protein Expression Profile of HT-29 Human Colon Cancer Cells after Treatment with a Cytotoxic Daunorubicin-GnRH-III Derivative Bioconjugate

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    <div><p>Targeted delivery of chemotherapeutic agents is a new approach for the treatment of cancer, which provides increased selectivity and decreased systemic toxicity. We have recently developed a promising drug delivery system, in which the anticancer drug daunorubicin (Dau) was attached <i>via</i> oxime bond to a gonadotropin-releasing hormone-III (GnRH-III) derivative used as a targeting moiety (Glp-His-Trp-Lys(Ac)-His-Asp-Trp-Lys(Dau = Aoa)-Pro-Gly-NH<sub>2</sub>; Glp = pyroglutamic acid, Ac = acetyl; Aoa = aminooxyacetyl). This bioconjugate exerted <i>in vitro</i> cytostatic/cytotoxic effect on human breast, prostate and colon cancer cells, as well as significant <i>in vivo</i> tumor growth inhibitory effect on colon carcinoma bearing mice. In our previous studies, H-Lys(Dau = Aoa)-OH was identified as the smallest metabolite produced in the presence of rat liver lysosomal homogenate, which was able to bind to DNA <i>in vitro</i>. To get a deeper insight into the mechanism of action of the bioconjugate, changes in the protein expression profile of HT-29 human colon cancer cells after treatment with the bioconjugate or free daunorubicin were investigated by mass spectrometry-based proteomics. Our results indicate that several metabolism-related proteins, molecular chaperons and proteins involved in signaling are differently expressed after targeted chemotherapeutic treatment, leading to the conclusion that the bioconjugate exerts its cytotoxic action by interfering with multiple intracellular processes.</p></div

    Structure representation of cytotoxic agents.

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    <p>(A) daunorubicin and (B) oxime bond-linked daunorubicin-GnRH-III derivative bioconjugate, GnRH-III[<sup>4</sup>Lys(Ac), <sup>8</sup>Lys(Dau = Aoa)].</p

    Protein expression profile of HT-29 human colon cancer cells.

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    <p>(A) untreated, (B) bioconjugate-treated and (C) daunorubicin-treated cancer cells. Shown only on the control gel, arrows and spot numbers indicate the significantly different protein spots.</p
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