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Sample records for conjugated anti-il-2 receptor

  1. Imaging GABAc Receptors with Ligand-Conjugated Quantum Dots

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    Ian D. Tomlinson

    2007-01-01

    Full Text Available We report a methodology for labeling the GABAc receptor on the surface membrane of intact cells. This work builds upon our earlier work with serotonin-conjugated quantum dots and our studies with PEGylated quantum dots to reduce nonspecific binding. In the current approach, a PEGylated derivative of muscimol was synthesized and attached via an amide linkage to quantum dots coated in an amphiphilic polymer derivative of a modified polyacrylamide. These conjugates were used to image GABAC receptors heterologously expressed in Xenopus laevis oocytes.

  2. Gastrin receptor-avid peptide conjugates

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    Hoffman, Timothy J.; Volkert, Wynn A.; Li, Ning; Sieckman, Gary; Higginbotham, Chrys-Ann

    2006-12-12

    A compound for use as a therapeutic or diagnostic radiopharmaceutical includes a group capable of complexing a medically useful metal attached to a moiety which is capable of binding to a gastrin releasing peptide receptor. A method for treating a subject having a neoplastic disease includes administering to the subject an effective amount of a radiopharmaceutical having a metal chelated with a chelating group attached to a moiety capable of binding to a gastrin releasing peptide receptor expressed on tumor cells with subsequent internalization inside of the cell. A method of forming a therapeutic or diagnostic compound includes reacting a metal synthon with a chelating group covalently linked with a moiety capable of binding a gastrin releasing peptide receptor.

  3. Gastrin Receptor-Avid Peptide Conjugates

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    Hoffman, Timothy J. (Columbia, MO); Volkert, Wynn A. (Columbia, MO); Li, Ning (Baltimore, MD); Sieckman, Gary (Ashland, MO); Higginbotham, Chrys-Ann (Columbia, MO)

    2005-07-26

    A compound for use as a therapeutic or diagnostic radiopharmaceutical includes a group capable of complexing a medically useful metal attached to a moiety which is capable of binding to a gastrin releasing peptide receptor. A method for treating a subject having a neoplastic disease includes administering to the subject an effective amount of a radiopharmaceutical having a metal chelated with a chelating group attached to a moiety capable of binding to a gastrin releasing peptide receptor expressed on tumor cells with subsequent internalization inside of the cell. A method of forming a therapeutic or diagnostic compound includes reacting a metal synthon with a chelating group covalently linked with a moiety capable of binding a gastrin releasing peptide receptor.

  4. Antibody-protein A conjugated quantum dots for multiplexed imaging of surface receptors in living cells.

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    Jin, Takashi; Tiwari, Dhermendra K; Tanaka, Shin-Ichi; Inouye, Yasushi; Yoshizawa, Keiko; Watanabe, Tomonobu M

    2010-11-01

    To use quantum dots (QDs) as fluorescent probes for receptor imaging, QD surface should be modified with biomolecules such as antibodies, peptides, carbohydrates, and small-molecule ligands for receptors. Among these QDs, antibody conjugated QDs are the most promising fluorescent probes. There are many kinds of coupling reactions that can be used for preparing antibody conjugated QDs. Most of the antibody coupling reactions, however, are non-selective and time-consuming. In this paper, we report a facile method for preparing antibody conjugated QDs for surface receptor imaging. We used ProteinA as an adaptor protein for binding of antibody to QDs. By using ProteinA conjugated QDs, various types of antibodies are easily attached to the surface of the QDs via non-covalent binding between the F(c) (fragment crystallization) region of antibody and ProteinA. To show the utility of ProteinA conjugated QDs, HER2 (anti-human epidermal growth factor receptor 2) in KPL-4 human breast cancer cells were stained by using anti-HER2 antibody conjugated ProteinA-QDs. In addition, multiplexed imaging of HER2 and CXCR4 (chemokine receptor) in the KPL-4 cells was performed. The result showed that CXCR4 receptors coexist with HER2 receptors in the membrane surface of KPL-4 cells. ProteinA mediated antibody conjugation to QDs is very useful to prepare fluorescent probes for multiplexed imaging of surface receptors in living cells.

  5. Controlling Androgen receptor nuclear localization by dendrimer conjugates

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    Wang, Haoyu

    Androgen Receptor (AR) antagonists, such as bicalutamide and flutamide have been used widely in the treatment of prostate cancer. Although initial treatment is effective, prostate cancer cells often acquire antiandrogen resistance with prolonged treatment. AR over-expression and AR mutations contribute to the development of antiandrogen resistant cancer. Second generation antiandrogens such as enzalutamide are more effective and show reduced AR nuclear localization. In this study, derivatives of PAN52, a small molecule antiandrogen previously developed in our lab, were conjugated to the surface of generation 4 and generation 6 PAMAM dendrimers to obtain antiandrogen PAMAM dendrimer conjugates (APDC). APDCs readily enter cells and associate with AR in the cytoplasm. Due to their large size and positive charge, they can not enter the nucleus, thus retaining AR in the cytoplasm. In addition, APDCs are effective in decreasing AR mediated transcription and cell proliferation. APDC is the first AR antagonists that inhibit DHT-induced nuclear localization of AR. By inhibiting AR nuclear localization, APDC represents a new class of antiandrogens that offer an alternative approach to addressing antiandrogen-resistant prostate cancer. Lysine post-translational modification of AR Nuclear Localization Sequence (NLS) has great impact on AR cellular localization. It is of interest to understand which modifications modulate AR translocation into the nucleus. In this study, we prepared dendrimer-based acetyltransferase mimetic (DATM), DATM is able to catalytically acetylate AR in CWR22Rv1 cells, which will be a useful tool for studying AR modification effect on AR cellular localization. Derivatives of DATM, which transfer other chemical groups to AR, can be prepared similarly, and with more dendrimer based AR modification tools prepared in future, we will be able to understand and control AR cellular localization through AR modification.

  6. Conjugation with receptor-targeted histidine-rich peptides enhances the pharmacological effectiveness of antisense oligonucleotides.

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    Nakagawa, Osamu; Ming, Xin; Carver, Kyle; Juliano, Rudy

    2014-01-15

    Ineffective delivery to intracellular sites of action is one of the key limitations to the use of antisense and siRNA oligonucleotides as therapeutic agents. Here, we describe molecular scale antisense oligonucleotide conjugates that bind selectively to a cell surface receptor, are internalized, and then partially escape from nonproductive endosomal locations to reach their sites of action in the nucleus. Peptides that include bombesin sequences for receptor targeting and a run of histidine residues for endosomal disruption were covalently linked to a splice switching antisense oligonucleotide. The conjugates were tested for their ability to correct splicing and up-regulate expression of a luciferase reporter in prostate cancer cells that express the bombesin receptor. We found that trivalent conjugates that included both the targeting sequence and several histidine residues were substantially more effective than conjugates containing only the bombesin or histidine moieties. This demonstrates the potential of creating molecular scale oligonucleotide conjugates with both targeting and endosome escape capabilities.

  7. Impact of linker and conjugation chemistry on antigen binding, Fc receptor binding and thermal stability of model antibody-drug conjugates.

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    Acchione, Mauro; Kwon, Hyewon; Jochheim, Claudia M; Atkins, William M

    2012-01-01

    Antibody-drug conjugates (ADCs) with biotin as a model cargo tethered to IgG1 mAbs via different linkers and conjugation methods were prepared and tested for thermostability and ability to bind target antigen and Fc receptor. Most conjugates demonstrated decreased thermostability relative to unconjugated antibody, based on DSC, with carbohydrate and amine coupled ADCs showing the least effect compared with thiol coupled conjugates. A strong correlation between biotin-load and loss of stability is observed with thiol conjugation to one IgG scaffold, but the stability of a second IgG scaffold is relatively insensitive to biotin load. The same correlation for amine coupling was less significant. Binding of antibody to antigen and Fc receptor was investigated using surface plasmon resonance. None of the conjugates exhibited altered antigen affinity. Fc receptor FcγIIb (CD32b) interactions were investigated using captured antibody conjugate. Protein G and Protein A, known inhibitors of Fc receptor (FcR) binding to IgG, were also used to extend the analysis of the impact of conjugation on Fc receptor binding. H10NPEG4 was the only conjugate to show significant negative impact to FcR binding, which is likely due to higher biotin-load compared with the other ADCs. The ADC aHISNLC and aHISTPEG8 demonstrated some loss in affinity for FcR, but to much lower extent. The general insensitivity of target binding and effector function of the IgG1 platform to conjugation highlight their utility. The observed changes in thermostability require consideration for the choice of conjugation chemistry, depending on the system being pursued and particular application of the conjugate.

  8. Folate receptor mediated intracellular protein delivery using PLL-PEG-FOL conjugate.

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    Hwa Kim, Sun; Hoon Jeong, Ji; Joe, Cheol O; Gwan Park, Tae

    2005-04-18

    To develop a receptor-mediated intracellular delivery system that can transport therapeutic proteins or other bioactive macromolecules into a specific cell, a di-block copolymer conjugate, poly(L-lysine)-poly(ethylene glycol)-folate (PLL-PEG-FOL), was synthesized. The PLL-PEG-FOL conjugate was physically complexed with fluorescein isothiocyanate conjugated bovine serum albumin (FITC-BSA) in an aqueous phase by ionic interactions. Cellular uptake of PLL-PEG-FOL/FITC-BSA complexes was greatly enhanced against a folate receptor over-expressing cell line (KB cells) compared to a folate receptor deficient cell line (A549 cells). The presence of an excess amount of free folate (1 mM) in the medium inhibited the intracellular delivery of PLL-PEG-FOL/FITC-BSA complexes. This suggests that the enhanced cellular uptake of FITC-BSA by KB cells in a specific manner was attributed to folate receptor-mediated endocytosis of the complexes having folate moieties on the surface. The PLL-PEG-FOL di-block copolymer could be potentially applied for intracellular delivery of a wide range of other biological active agents that have negative charges on the surface.

  9. Folate Receptor-Targeted Dendrimer-Methotrexate Conjugate for Inflammatory Arthritis.

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    Qi, Rong; Majoros, Istvan; Misra, Asish C; Koch, Alisa E; Campbell, Phil; Marotte, Hubert; Bergin, Ingrid L; Cao, Zhengyi; Goonewardena, Sascha; Morry, Jingga; Zhang, Shuai; Beer, Michael; Makidon, Paul; Kotlyar, Alina; Thomas, Thommey P; Baker, James R

    2015-08-01

    Generation 5 (G5) poly(amidoamide) (PAMAM) dendrimers are synthetic polymers that have been broadly applied as drug delivery carriers. Methotrexate (MTX), an anti-folate metabolite, has been successfully used as an anti-inflammatory drug to treat rheumatoid arthritis (RA) in the clinic. In this study, we examine the therapeutic efficacy of G5 PAMAM dendrimer methotrexate conjugates (G5-MTX) that also have folic acid (FA) conjugated to the G5-MTX (G5-FA-MTX) to target inflammation-activated folate receptors overexpressing macrophages. These cells are thought to play an important role in the development of RA. With G5 serving as a control, the in vitro binding affinities of G5-FA-MTX and G5-MTX to activated macrophages were assessed in RAW264.7, NR8383 and primary rat peritoneal macrophages. The results indicated that the binding of either conjugate to macrophages was concentration- and temperature-dependent and could be blocked by the presence of 6.25 mM free FA (p < 0.005). The preventive effects of G5-MTX and G5-FA-MTX conjugates on the development of arthritis were explored on an adjuvant-induced inflammatory arthritis model and had similar preventive effects in inflammatory arthritis at a MTX equivalent dose of 4.95 μmol/kg. These studies indicated that when multiples of MTX are conjugated on dendritic polymers, they specifically bind to folate receptor overexpressing macrophages and have comparable anti-inflammatory effects to folate targeted MTX conjugated polymers.

  10. Lanreotide-conjugated PEG-DSPE micelles: an efficient nanocarrier targeting to somatostatin receptor positive tumors.

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    Zheng, Nan; Dai, Wenbing; Zhang, Hua; Wang, Xueqing; Wang, Jiancheng; Zhang, Xuan; Wang, Kun; Li, Jian; Zhang, Qiang

    2015-01-01

    Lanreotide is an octapeptide analog of endogenous somatostatin, specifically binding with tumors over-express somatostatin receptor 2 (SSTR2). In this study, we conjugated lanreotide to 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (poly-(ethylene glycol))-2000] (PEG-DSPE), constructed active targeted micelles (lanreotide-PM), characterized their in vitro and in vivo targeting effect, and explored the receptor mediated transportion. The uptake of lanreotide-PM was found to be related to the expression level of SSTR2 in different cell lines and the competitive inhibition phenomenon indicated that the cellular uptake of lanreotide-PM was via a receptor meditated mechanism. In vivo, more lanreotide-PM accumulated in SSTR2 high expression tumor xenografts, endocytosed by the tumor cells, induced more apoptosis of tumor cells, and suppressed tumor growth efficiently. In conclusion, lanreotide-modified micelles containing antitumor drugs provide a promising strategy for the treatment of SSTR-expressing tumors.

  11. Enhanced A3 adenosine receptor selectivity of multivalent nucleoside-dendrimer conjugates

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    Shainberg Asher

    2008-10-01

    Full Text Available Abstract Background An approach to use multivalent dendrimer carriers for delivery of nucleoside signaling molecules to their cell surface G protein-coupled receptors (GPCRs was recently introduced. Results A known adenosine receptor (AR agonist was conjugated to polyamidoamine (PAMAM dendrimer carriers for delivery of the intact covalent conjugate to on the cell surface. Depending on the linking moiety, multivalent conjugates of the N6-chain elongated functionalized congener ADAC (N6-[4-[[[4-[[[(2-aminoethylamino]carbonyl]methyl]anilino]carbonyl]methyl]phenyl]-adenosine achieved unanticipated high selectivity in binding to the cytoprotective human A3 AR, a class A GPCR. The key to this selectivity of > 100-fold in both radioreceptor binding (Ki app = 2.4 nM and functional assays (EC50 = 1.6 nM in inhibition of adenylate cyclase was maintaining a free amino group (secondary in an amide-linked chain. Attachment of neutral amide-linked chains or thiourea-containing chains preserved the moderate affinity and efficacy at the A1 AR subtype, but there was no selectivity for the A3 AR. Since residual amino groups on dendrimers are associated with cytotoxicity, the unreacted terminal positions of this A3 AR-selective G2.5 dendrimer were present as carboxylate groups, which had the further benefit of increasing water-solubility. The A3 AR selective G2.5 dendrimer was also visualized binding the membrane of cells expressing the A3 receptor but did not bind cells that did not express the receptor. Conclusion This is the first example showing that it is feasible to modulate and even enhance the pharmacological profile of a ligand of a GPCR based on conjugation to a nanocarrier and the precise structure of the linking group, which was designed to interact with distal extracellular regions of the 7 transmembrane-spanning receptor. This ligand tool can now be used in pharmacological models of tissue rescue from ischemia and to probe the existence of A3 AR

  12. Targeting of peptide conjugated magnetic nanoparticles to urokinase plasminogen activator receptor (uPAR) expressing cells

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    Hansen, Line; Unmack Larsen, Esben Kjær; Nielsen, Erik Holm; Iversen, Frank; Liu, Zhuo; Thomsen, Karen; Pedersen, Michael; Skrydstrup, Troels; Nielsen, Niels Chr.; Ploug, Michael; Kjems, Jørgen

    2013-08-01

    Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor patient prognosis shared by several cancers including breast, colorectal, and gastric cancers. Conjugation of a uPAR specific targeting peptide onto polyethylene glycol (PEG) coated USPIO nanoparticles by click chemistry resulted in a five times higher uptake in vitro in a uPAR positive cell line compared to nanoparticles carrying a non-binding control peptide. In accordance with specific receptor-mediated recognition, a low uptake was observed in the presence of an excess of ATF, a natural ligand for uPAR. The uPAR specific magnetic nanoparticles can potentially provide a useful supplement for tumor patient management when combined with MRI and drug delivery.Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor patient prognosis shared by several cancers including breast, colorectal, and gastric cancers. Conjugation of a uPAR specific

  13. Quantitative analysis of agonist-dependent parathyroid hormone receptor trafficking in whole cells using a functional green fluorescent protein conjugate.

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    Conway, B R; Minor, L K; Xu, J Z; D'Andrea, M R; Ghosh, R N; Demarest, K T

    2001-12-01

    Many G-protein coupled receptors (GPCRs) undergo ligand-dependent internalization upon activation. The parathyroid hormone (PTH) receptor undergoes endocytosis following prolonged exposure to ligand although the ultimate fate of the receptor following internalization is largely unknown. To investigate compartmentalization of the PTH receptor, we have established a stable cell line expressing a PTH receptor-green fluorescent protein (PTHR-GFP) conjugate and an algorithm to quantify PTH receptor internalization. HEK 293 cells expressing the PTHR-GFP were compared with cells expressing the wild-type PTH receptor in whole-cell binding and functional assays. 125I-PTH binding studies revealed similar Bmax and kD values in cells expressing either the PTHR-GFP or the wild-type PTH receptor. PTH-induced cAMP accumulation was similar in both cell lines suggesting that addition of the GFP to the cytoplasmic tail of the PTH receptor does not alter the ligand binding or G-protein coupling properties of the receptor. Using confocal fluorescence microscopy, we demonstrated that PTH treatment of cells expressing the PTHR-GFP conjugate produced a time-dependent redistribution of the receptor to the endosomal compartment which was blocked by pretreatment with PTH antagonist peptides. Treatment with hypertonic sucrose prevented PTH-induced receptor internalization, suggesting that the PTH receptor internalizes via a clathrin-dependent mechanism. Moreover, co-localization with internalized transferrin showed that PTHR-GFP trafficking utilized the endocytic recycling compartment. Experiments using cycloheximide to inhibit protein synthesis demonstrated that recycling of the PTHR-GFP back to the plasma membrane was complete within 1-2 h of ligand removal and was partially blocked by pretreatment with cytochalasin D, but not nocodazole. We also demonstrated that the PTH receptor, upon recycling to the plasma membrane, is capable of undergoing a second round of internalization, a finding

  14. Non-covalent conjugates of single-walled carbon nanotubes and folic acid for interaction with cells overexpressing folate receptors

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    Castillo, John J.; Rindzevicius, Tomas; Novoa, Leidy V.

    2013-01-01

    We here present amethod to form a noncovalent conjugate of single-walled carbon nanotubes and folic acid aimed to interact with cells over-expressing folate receptors. The bonding was obtained without covalent chemical functionalization using a simple, rapid “one pot” synthesis method. The zeta p...

  15. Design and characteristics of cytotoxic fibroblast growth factor 1 conjugate for fibroblast growth factor receptor-targeted cancer therapy

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    Szlachcic A

    2016-08-01

    Full Text Available Anna Szlachcic, Malgorzata Zakrzewska, Michal Lobocki, Piotr Jakimowicz, Jacek Otlewski Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland Abstract: Fibroblast growth factor receptors (FGFRs are attractive candidate cancer therapy targets as they are overexpressed in multiple types of tumors, such as breast, prostate, bladder, and lung cancer. In this study, a natural ligand of FGFR, an engineered variant of fibroblast growth factor 1 (FGF1V, was conjugated to a potent cytotoxic drug, monomethyl auristatin E (MMAE, and used as a targeting agent for cancer cells overexpressing FGFRs, similar to antibodies in antibody–drug conjugates. The FGF1V–valine–citrulline–MMAE conjugate showed a favorable stability profile, bound FGFRs on the cell surface specifically, and efficiently released the drug (MMAE upon cleavage by the lysosomal protease cathepsin B. Importantly, the conjugate showed a prominent cytotoxic effect toward cell lines expressing FGFR. FGF1V–vcMMAE was highly cytotoxic at concentrations even an order of magnitude lower than those found for free MMAE. This effect was FGFR-specific as cells lacking FGFR did not show any increased mortality. Keywords: fibroblast growth factor 1, FGF receptor, targeted cancer therapy, cytotoxic conjugates, FGFR-dependent cancer, MMAE, auristatin

  16. Novel Selective Estrogen Receptor Ligand Conjugates Incorporating Endoxifen-Combretastatin and Cyclofenil-Combretastatin Hybrid Scaffolds: Synthesis and Biochemical Evaluation

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    Patrick M. Kelly

    2017-08-01

    Full Text Available Nuclear receptors such as the estrogen receptors (ERα and ERβ modulate the effects of the estrogen hormones and are important targets for design of innovative chemotherapeutic agents for diseases such as breast cancer and osteoporosis. Conjugate and bifunctional compounds which incorporate an ER ligand offer a useful method of delivering cytotoxic drugs to tissue sites such as breast cancers which express ERs. A series of novel conjugate molecules incorporating both the ER ligands endoxifen and cyclofenil-endoxifen hybrids covalently linked to the antimitotic and tubulin targeting agent combretastatin A-4 were synthesised and evaluated as ER ligands. A number of these compounds demonstrated pro-apoptotic effects, with potent antiproliferative activity in ER-positive MCF-7 breast cancer cell lines and low cytotoxicity. These conjugates displayed binding affinity towards ERα and ERβ isoforms at nanomolar concentrations e.g., the cyclofenil-amide compound 13e is a promising lead compound of a clinically relevant ER conjugate with IC50 in MCF-7 cells of 187 nM, and binding affinity to ERα (IC50 = 19 nM and ERβ (IC50 = 229 nM while the endoxifen conjugate 16b demonstrates antiproliferative activity in MCF-7 cells (IC50 = 5.7 nM and binding affinity to ERα (IC50 = 15 nM and ERβ (IC50 = 115 nM. The ER binding effects are rationalised in a molecular modelling study in which the disruption of the ER helix-12 in the presence of compounds 11e, 13e and 16b is presented These conjugate compounds have potential application for further development as antineoplastic agents in the treatment of ER positive breast cancers.

  17. Chlorin e6 Conjugated Interleukin-6 Receptor Aptamers Selectively Kill Target Cells Upon Irradiation

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    Sven Kruspe

    2014-01-01

    Full Text Available Photodynamic therapy (PDT uses the therapeutic properties of light in combination with certain chemicals, called photosensitizers, to successfully treat brain, breast, prostate, and skin cancers. To improve PDT, current research focuses on the development of photosensitizers to specifically target cancer cells. In the past few years, aptamers have been developed to directly deliver cargo molecules into target cells. We conjugated the photosensitizer chlorin e6 (ce6 with a human interleukin-6 receptor (IL-6R binding RNA aptamer, AIR-3A yielding AIR-3A-ce6 for application in high efficient PDT. AIR-3A-ce6 was rapidly and specifically internalized by IL-6R presenting (IL-6R+ cells. Upon light irradiation, targeted cells were selectively killed, while free ce6 did not show any toxic effect. Cells lacking the IL-6R were also not affected by AIR-3A-ce6. With this approach, we improved the target specificity of ce6-mediated PDT. In the future, other tumor-specific aptamers might be used to selectively localize photosensitizers into cells of interest and improve the efficacy and specificity of PDT in cancer and other diseases.

  18. Steroid Probes Conjugated with Protein-Protected Gold Nanocluster: Specific and Rapid Fluorescence Imaging of Steroid Receptors in Target Cells.

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    Tsai, Chi-Yan; Li, Chun-Wei; Li, Jie-Ren; Jang, Bo-Han; Chen, Shu-Hui

    2016-07-01

    Steroid ligands can easily diffuse through the cell membrane and this property makes it feasible to be used for in-situ staining of the nuclear receptors. However, nonspecific binding of the internalized ligand probe with the cellular components has caused serious interferences for the detection of receptor-expressing cells. We report a novel gold nanocluster (AuNC)-conjugated estrogen probe that can eliminate nonspecific internalization and accelerate nuclear localization to achieve selective and rapid detection of estrogen receptors (ERs) in live cells. The AuNC, protected by bovine serum albumin (BSA), BSA-AuNCs, was prepared by the synthesis and confirmed to be 1.9 nm in core size and 18 nm in diameter. Ethinyl estradiol was used as the precursor of 17β-estradial (E2) to conjugate with BSA-protected AuNCs via polyethylene glycol linker (E2-PEG/BSA-AuNCs) or to conjugate with Cy3 dyes (E2-Cy3). The conjugated probe was determined to contain five E2 molecules per BSA-AuNC by mass spectrometry and exhibit an emission maximum of around 640 nm, which was not altered by E2 conjugation indicating that the structural integrity of BSA-AuNCs was conserved. E2-PEG/BSA-AuNCs probes were quickly internalized by MCF-7 (ER+) cells and localized to the nuclei in 2 h. Such internalization was sensitive to competition by free E2 and was rarely detected in the controls using either non-conjugated BSA-AuNCs in MCF-7 (ER+) cells or E2-PEG/BSA-AuNCs in MDA-MB-231 (ER-) cells. In contrast to the high specificity of E2-PEG/BSA-AuNCs probe, the uptake of E2-Cy3 probe could not differentiate between MCF-7(ER+) and MDA-MB-231(ER-) cells during the early phases of the treatment. Moreover, nuclear targeting by E2-Cy3 was three times slower than that by the E2-PEG/BSA-AuNC probe. Such accelerated nuclei targeting was consistent with the enhanced cell viability by conjugating E2 with BSA-AuNC. In conclusion, the E2-PEG/BSA-AuNC probes are promising candidates that can be used for the

  19. Enhanced toxicity and cellular uptake of methotrexate-conjugated nanoparticles in folate receptor-positive cancer cells by decorating with folic acid-conjugated d-α-tocopheryl polyethylene glycol 1000 succinate.

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    Junyaprasert, Varaporn Buraphacheep; Dhanahiranpruk, Sirithip; Suksiriworapong, Jiraphong; Sripha, Kittisak; Moongkarndi, Primchanien

    2015-12-01

    Folic acid-conjugated d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS-FOL) decorated methotrexate (MTX)-conjugated nanoparticles were developed for targeted delivery of MTX to folate receptor-expressed tumor cells. The synthesis of TPGS-FOL followed 3-step process. Firstly, the terminal hydroxyl group of TPGS was converted to sulfonyl chloride using mesyl chloride in comparison with nosyl and tosyl chlorides. The highest conversion efficiency and yield were obtained by mesyl chloride due to the formation of higher reactive intermediate in a presence of triethylamine. Secondly, the substitution of sulfonyl group by sodium azide produced considerably high yield with conversion efficiency of over 90%. Lastly, the coupling reaction of azido-substituted TPGS and propargyl folamide by click reaction resulted in 96% conjugation efficiency without polymer degradation. To fabricate the folate receptor-targeted nanoparticles, 10 and 20%mol MTX-conjugated PEGylated poly(ϵ-caprolactone) nanoparticles were decorated with TPGS-FOL. The size and size distribution of MTX-conjugated nanoparticles relatively increased with %MTX. The MTX release from the nanoparticles was accelerated in acidic medium with an increase of %MTX but retarded in physiological pH medium. The decoration of TPGS-FOL onto the nanoparticles slightly enlarged the size and size distribution of the nanoparticles; however, it did not affect the surface charge. The cytotoxicity and cellular uptake of MCF-7 cells demonstrated that 10% MTX-conjugated nanoparticles and FOL-decorated nanoparticles possessed higher toxicity and uptake efficiency than 20% MTX-conjugated nanoparticles and undecorated nanoparticles, respectively. The results indicated that FOL-10% MTX-conjugated nanoparticles exhibited potential targeted delivery of MTX to folate receptor-expressed cancer cells.

  20. Targeting of the prostacyclin specific IP1 receptor in lungs with molecular conjugates comprising prostaglandin I2 analogues.

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    Geiger, Johannes; Aneja, Manish K; Hasenpusch, Günther; Yüksekdag, Gülnihal; Kummerlöwe, Grit; Luy, Burkhard; Romer, Tina; Rothbauer, Ulrich; Rudolph, Carsten

    2010-04-01

    Molecular conjugates comprising targeting ligands hold great promise for site-specific gene delivery to distant tumors and individual organs including the lung. Here we show that prostaglandin I2 analogues can be used to improve gene transfer efficiency of polyethylenimine (PEI) gene vectors on bronchial and alveolar epithelial cells in vitro and lungs of mice in vivo. Prostacyclin (IP1) receptor expression was confirmed in pulmonary epithelial cell lines by western blot. Iloprost (ILO) and treprostinil (TRP), two prostaglandin I2 analogues, were conjugated to fluorescein-labeled BSA (FLUO-BSA) and compared for IP1 receptor binding/uptake in different lung cell lines. Binding of FLUO-BSA-ILO was 2-4-fold higher than for FLUO-BSA-TRP and could be specifically inhibited by free ILO and IP1 receptor antagonist CAY10449. Internalization of FLUO-BSA-ILO was confirmed by confocal microscopy. Molecular conjugates of PEI and ILO (PEI-g-ILO) were synthesized with increasing coupling degree (F(ILO) (ILO:PEI) = 2, 5, 8, 16) and analyzed for DNA binding, particle formation and transfection efficiency. At optimized conditions (N/P 4, F(ILO) = 5), gene expression using PEI-g-ILO was significantly up to 46-fold higher than for PEI gene vectors and specifically inhibited by CAY10449. Gene expression in the lungs of mice after aerosol delivery was 14-fold higher with PEI-g-ILO F(ILO) = 5 than for PEI. We suggest that targeting of IP1 receptor using ILO represents a promising approach to improve pulmonary gene transfer.

  1. Polymeric nanoparticles conjugate a novel heptapeptide as an epidermal growth factor receptor-active targeting ligand for doxorubicin

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    Liu CW

    2012-08-01

    Full Text Available Chia Wen Liu,1,2 Wen Jen Lin11Graduate Institute of Pharmaceutical Sciences, College of Medicine, National Taiwan University, Taipei; 2Drug Delivery Department, Biomedical Engineering Research Laboratories, Industrial Technology Research Institute, Hsinchu, TaiwanBackground: This study was performed to develop a functional poly(D,L-lactide-co-glycolide-poly(ethylene glycol (PLGA-PEG-bearing amino-active end group for peptide conjugation.Methods and results: PLGA was preactivated following by copolymerization with PEG diamine. The resulting amphiphilic PLGA-PEG copolymer bearing 97.0% of amino end groups had a critical micelle concentration of 3.0 × 10-8 mol/L, and the half-effective inhibition concentration (IC50 of the prepared PLGA-PEG nanoparticles was >100 mg/mL, which was much higher than that of PLGA nanoparticles (1.02 ± 0.37 mg/mL. The amphiphilic properties of PLGA-PEG spontaneously formed a core-shell conformation in the aqueous environment, and this special feature provided the amino group on the PEG chain scattered on the surface of PLGA-PEG nanoparticles for efficient peptide conjugation. The peptide-conjugated PLGA-PEG nanoparticles showed three-fold higher uptake than peptide-free PLGA-PEG nanoparticles in a SKOV3 cell line with high expression of epidermal growth factor receptor. Both peptide-conjugated and peptide-free PLGA-PEG nanoparticles were used as nanocarriers for delivery of doxorubicin. Although the rate of release of doxorubicin from both nanoparticles was similar, drug release at pH 4.0 (500 U lipase was faster than at pH 7.4. The IC50 of doxorubicin-loaded peptide-conjugated PLGA-PEG nanoparticles in SKOV3 cells (0.05 ± 0.03 µg/mL was much lower (by 62.4-fold than that of peptide-free PLGA-PEG nanoparticles (3.12 ± 1.44 µg/mL.Conclusion: This in vivo biodistribution study in SKOV3 tumor-bearing mice was further promising in that accumulation of doxorubicin in tumor tissue was in the order of peptide-conjugated

  2. Site-selective conjugation of an anticoagulant aptamer to recombinant albumins and maintenance of neonatal Fc receptor binding

    Science.gov (United States)

    Schmøkel, Julie; Voldum, Anders; Tsakiridou, Georgia; Kuhlmann, Matthias; Cameron, Jason; Sørensen, Esben S.; Wengel, Jesper; Howard, Kenneth A.

    2017-05-01

    Aptamers are an attractive molecular medicine that offers high target specificity. Nucleic acid-based aptamers, however, are prone to nuclease degradation and rapid renal excretion that require blood circulatory half-life extension enabling technologies. The long circulatory half-life, predominately facilitated by engagement with the cellular recycling neonatal Fc receptor (FcRn), and ligand transport properties of albumin promote it as an attractive candidate to improve the pharmacokinetic profile of aptamers. This study investigates the effect of Cys34 site-selective covalent attachment of a factor IXa anticoagulant aptamer on aptamer functionality and human FcRn (hFcRn) engagement using recombinant human albumin (rHA) of either a wild type (WT) or an engineered human FcRn high binding variant (HB). Albumin-aptamer conjugates, connected covalently through a heterobifunctional succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate linker, were successfully prepared and purified by high performance liquid chromatography as confirmed by gel electrophoresis band-shift analysis and matrix-assisted laser desorption/ionization time of flight. Minimal reduction (∼25%) in activity of WT-linked aptamer to that of aptamer alone was found using an anticoagulant activity assay measuring temporal levels of activated partial thrombin. Covalent albumin-aptamer conjugation, however, substantially compromized binding to hFcRn, to 10% affinity of that of non-conjugated WT, determined by biolayer interferometry. Binding could be rescued by aptamer conjugation to recombinant albumin engineered for higher FcRn affinity (HB) that exhibited an 8-fold affinity compared to WT alone. This work describes a novel albumin-based aptamer delivery system whose hFcRn binding can be increased using a HB engineered albumin.

  3. Synthesis and evaluation of a technetium-99m labeled cytotoxic bombesin peptide conjugate for targeting bombesin receptor-expressing tumors

    Energy Technology Data Exchange (ETDEWEB)

    Okarvi, Subhani M. [Cyclotron and Radiopharmaceuticals Department, King Faisal Specialist Hospital and Research Centre, MBC-03, PO Box 3354, Riyadh 11211 (Saudi Arabia)], E-mail: sokarvi@kfshrc.edu.sa; Al Jammaz, Ibrahim [Cyclotron and Radiopharmaceuticals Department, King Faisal Specialist Hospital and Research Centre, MBC-03, PO Box 3354, Riyadh 11211 (Saudi Arabia)

    2010-04-15

    Conjugation of the cytotoxic drugs to receptor-binding peptides is an attractive approach for the targeted delivery of cytotoxic peptide conjugates to tumor cells. In an attempt to develop an efficient peptide-based radiopharmaceutical for targeting bombesin (BN) receptor-expressing tumors (i.e., breast and prostate), we have prepared by solid-phase peptide synthesis, a novel BN analog derived from the universal sequence of BN and conjugated to a widely characterized antineoplastic agent, methotrexate (MTX). MTX-BN, after radiolabeling with {sup 99m}Tc via stannous-tartrate exchange, showed a good stability against cysteine and histidine transchelation as well as a high in vitro metabolic stability in human plasma. In vitro cell-binding and internalization on MDA-MB-231, MCF-7, T47-D breast cancer and PC-3 prostate cancer cell lines demonstrated high affinity and specificity of {sup 99m}Tc-MTX-BN towards both human breast and prostate cancer cells (binding affinities in nanomolar range). In addition, the radioconjugate displayed a significant internalization (values ranged between 19-35%) into the tumor cells. In vivo biodistribution and clearance kinetics in Balb/c mice are characterized by an efficient clearance from the blood and excretion mainly through the renal-urinary pathway with some elimination via the hepatobiliary system. In vivo tumor uptake in nude mice bearing MDA-MB-231 cells was 2.70{+-}0.44% ID/g at 1 h, whereas in nude mice with human epidermoid KB cells the accumulation in the tumor was found to be 1.48{+-}0.31% ID/g at 1 h post injection. The tumor uptake was always higher than in the blood and muscle, with good tumor retention and good tumor-to-blood and tumor-to-muscle ratios. The accumulation/retention in the major organs (i.e., lungs, stomach, liver, intestines, etc.) was low to moderate (<6% ID/g) in both healthy and tumor-bearing mice. However, the uptake/retention in the kidneys was rather high (up to 11.05{+-}1.80% ID/g), which is of a

  4. Synthesis and biological evaluation of (68) Ga-labeled Pteroyl-Lys conjugates for folate receptor-targeted tumor imaging.

    Science.gov (United States)

    Zhang, Xuran; Yu, Qian; He, Yingfang; Zhang, Chun; Zhu, Hua; Yang, Zhi; Lu, Jie

    2016-07-01

    In order to develop novel (68) Ga-labeled PET tracers for folate receptor imaging, two DOTA-conjugated Pteroyl-Lys derivatives, Pteroyl-Lys-DOTA and Pteroyl-Lys-DAV-DOTA, were designed, synthesized and radiolabeled with (68) Ga. Biological evaluations of the two radiotracers were performed with FR-positive KB cell line and athymic nude mice bearing KB tumors. Both (68) Ga-DOTA-Lys-Pteroyl and (68) Ga-DOTA-DAV-Lys-Pteroyl exhibited receptor specific binding in KB cells in vitro. The tumor uptake values of (68) Ga-DOTA-Lys-Pteroyl and (68) Ga-DOTA-DAV-Lys-Pteroy were 10.06 ± 0.59%ID/g and 11.05 ± 0.60%ID/g at 2 h post-injection, respectively. Flank KB tumor was clearly visualized with (68) Ga-DOTA-DAV-Lys-Pteroyl by Micro-PET imaging at 2 h post-injection, suggesting the feasibility of using (68) Ga-labeled Pteroyl-Lys conjugates as a novel class of FR targeted probes.

  5. Targeting of peptide conjugated magnetic nanoparticles to urokinase plasminogen activator receptor (uPAR) expressing cells

    DEFF Research Database (Denmark)

    Hansen, Line; Unmack Larsen, Esben Kjær; Nielsen, Erik Holm

    2013-01-01

    Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted...... towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor...... to nanoparticles carrying a non-binding control peptide. In accordance with specific receptor-mediated recognition, a low uptake was observed in the presence of an excess of ATF, a natural ligand for uPAR. The uPAR specific magnetic nanoparticles can potentially provide a useful supplement for tumor patient...

  6. Receptor-mediated hepatic uptake of M6P-BSA-conjugated triplex-forming oligonucleotides in rats.

    Science.gov (United States)

    Ye, Zhaoyang; Cheng, Kun; Guntaka, Ramareddy V; Mahato, Ram I

    2006-01-01

    Excessive production of extracellular matrix, predominantly type I collagen, results in liver fibrosis. Earlier we synthesized mannose 6-phosphate-bovine serum albumin (M6P-BSA) and conjugated to the type I collagen specific triplex-forming oligonucleotide (TFO) for its enhanced delivery to hepatic stellate cells (HSCs), which is the principal liver fibrogenic cell. In this report, we demonstrate a time-dependent cellular uptake of M6P-BSA-33P-TFO by HSC-T6 cells. Both cellular uptake and nuclear deposition of M6P-BSA-33P-TFO were significantly higher than those of 33P-TFO, leading to enhanced inhibition of type I collagen transcription. Following systemic administration into rats, hepatic accumulation of M6P-BSA-33P-TFO increased from 55% to 68% with the number of M6P per BSA from 14 to 27. Unlike 33P-TFO, there was no significant decrease in the hepatic uptake of (M6P)20-BSA-33P-TFO in fibrotic rats. Prior administration of excess M6P-BSA decreased the hepatic uptake of (M6P)20-BSA-33P-TFO from 66% to 40% in normal rats, and from 60% to 15% in fibrotic rats, suggesting M6P/insulin-like growth factor II (M6P/IGF II) receptor-mediated endocytosis of M6P-BSA-33P-TFO by HSCs. Almost 82% of the total liver uptake in fibrotic rats was contributed by HSCs. In conclusion, by conjugation with M6P-BSA, the TFO could be potentially used for the treatment of liver fibrosis.

  7. In vivo imaging of folate receptor positive tumor xenografts using novel 68Ga-NODAGA-folate conjugates.

    Science.gov (United States)

    Fani, Melpomeni; Tamma, Maria-Luisa; Nicolas, Guillaume P; Lasri, Elisabeth; Medina, Christelle; Raynal, Isabelle; Port, Marc; Weber, Wolfgang A; Maecke, Helmut R

    2012-05-07

    The overexpression of the folate receptor (FR) in a variety of malignant tumors, along with its limited expression in healthy tissues, makes it an attractive tumor-specific molecular target. Noninvasive imaging of FR using radiolabeled folate derivatives is therefore highly desirable. Given the advantages of positron emission tomography (PET) and the convenience of (68)Ga production, the aim of our study was to develop a new (68)Ga-folate-based radiotracer for clinical application. The chelator 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA) was conjugated to folic acid and to 5,8-dideazafolic acid using 1,2-diaminoethane as a spacer, resulting in two novel conjugates, namely, P3246 and P3238, respectively. Both conjugates were labeled with (68/67)Ga. In vitro internalization, efflux, and saturation binding studies were performed using the FR-positive KB cell line. Biodistribution and small-animal PET imaging studies were performed in nude mice bearing subcutaneous KB xenografts. Both conjugates were labeled with (68)Ga at room temperature within 10 min in labeling yields >95% and specific activity ~30 GBq/μmol. The K(d) values of (68/67)Ga-P3246 (5.61 ± 0.96 nM) and (68/67)Ga-P3238 (7.21 ± 2.46 nM) showed high affinity for the FR. (68/67)Ga-P3246 showed higher cell-associated uptake in vitro than (68/67)Ga-P3238 (approximately 72 and 60% at 4 h, respectively, P 68)Ga-P3246 and (68)Ga-P3238 (16.56 ± 3.67 and 10.95 ± 2.12% IA/g, respectively, P > 0.05) and remained at about the same level up to 4 h. Radioactivity also accumulated in the FR-positive organs, such as kidneys (91.52 ± 21.05 and 62.26 ± 14.32% IA/g, respectively, 1 h pi) and salivary glands (9.05 ± 2.03 and 10.39 ± 1.19% IA/g, respectively, 1 h pi). The specificity of the radiotracers for the FR was confirmed by blocking experiments where tumor uptake was reduced by more than 85%, while the uptake in the kidneys and the salivary glands was reduced by more than 90%. Reduction of

  8. A Novel Molecular Fluorescent Technique for Imaging the Somatostatin Receptor 2, Using a DOTATOC Lanthanide Conjugate

    DEFF Research Database (Denmark)

    Andersen, Rune Wiik; Prakash, Vineet; Stensballe, Allan

    to easily obtain commercial receptor antibodies. We propose an alternative with the novel use of lanthanide fluorescent DOTATOC imaging.Purpose is to prove that it is feasible to combine the fluorescent nuclear imaging of neuroendocrine tumors with histopathological correlates using the same bio......-functional DOTATOC component.                       METHOD AND MATERIALS            The chelation of Europium and Samarium to DOTATOC was proven using MALDI-TOF Mass Spectrometry. The rise in quantum yield between unchelated lanthanides and those bound by DOTATOC was examined using fluorescence spectroscopy...

  9. The conjugated linoleic acid isomer trans-9,trans-11 is a dietary occurring agonist of liver X receptor {alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Ecker, Josef; Liebisch, Gerhard [Institute of Clinical Chemistry, University of Regensburg (Germany); Patsch, Wolfgang [Department of Laboratory Medicine, Hospital of Salzburg (Austria); Schmitz, Gerd, E-mail: gerd.schmitz@klinik.uni-regensburg.de [Institute of Clinical Chemistry, University of Regensburg (Germany)

    2009-10-30

    Conjugated linoleic acid (CLA) isomers are dietary fatty acids that modulate gene expression in many cell types. We have previously reported that specifically trans-9,trans-11 (t9,t11)-CLA induces expression of genes involved in lipid metabolism of human macrophages. To elucidate the molecular mechanism underlying this transcriptional activation, we asked whether t9,t11-CLA affects activity of liver X receptor (LXR) {alpha}, a major regulator of macrophage lipid metabolism. Here we show that t9,t11-CLA is a regulator of LXR{alpha}. We further demonstrate that the CLA isomer induces expression of direct LXR{alpha} target genes in human primary macrophages. Knockdown of LXR{alpha} with RNA interference in THP-1 cells inhibited t9,t11-CLA mediated activation of LXR{alpha} including its target genes. To evaluate the effective concentration range of t9,t11-CLA, human primary macrophages were treated with various doses of CLA and well known natural and synthetic LXR agonists and mRNA expression of ABCA1 and ABCG1 was analyzed. Incubation of human macrophages with 10 {mu}M t9,t11-CLA led to a significant modulation of ABCA1 and ABCG1 transcription and caused enhanced cholesterol efflux to high density lipoproteins and apolipoprotein AI. In summary, these data show that t9,t11-CLA is an agonist of LXR{alpha} in human macrophages and that its effects on macrophage lipid metabolism can be attributed to transcriptional regulations associated with this nuclear receptor.

  10. Carboxymethyl-β-cyclodextrin conjugated nanoparticles facilitate therapy for folate receptor-positive tumor with the mediation of folic acid.

    Science.gov (United States)

    Su, Chang; Li, Hongdan; Shi, Yijie; Wang, Guan; Liu, Liwei; Zhao, Liang; Su, Rongjian

    2014-10-20

    Currently, clinical operation treatments, chemotherapy and radiotherapy just could eliminate local tumor cells. However, chemotherapy and radiotherapy also injury normal cells and lead to serious side effects and toxicities. So, it is necessary to find an effective target cancer carrier that delivers the anticancer agents into tumor cells and reduces normal cells' injury. Folic acid (FA) is a classical targeting agent mediates internalization of chemical drugs into tumor cells which over-express folate receptor (FR) on their surface. We herein report that based on host-guest interaction, NPs decorated by novel folate enhance antitumor drug delivery. BSA-NPs were prepared by desolvation method and carboxymethyl-β-cyclodextrin (CM-β-CD) was conjugated to the surface of NPs by carbodiimide coupling to hold FA. From in vitro cytotoxicity assay, cell apoptosis study, intracellular ATP level assay and western blot, we can see that FA-CM-β-CD-BSA NPs as good monodispersity, negative charge, and homogenous particle size have a high encapsulation efficiency. The results showed that MTT and cell apoptosis demonstrated that FA-decorated NPs exhibit stronger inhibition rate and induce obvious apoptosis in FR positive Hela cells as compared to free drug and FA undecorated NPs. Moreover, 5-fluorouracil (5-Fu) loaded FA-CM-β-CD-BSA NPs down-regulate ATP levels and increase the expression of caspase-3. Taken together, FA-CM-β-CD-BSA NPs enhance FR receptor-mediated endocytosis and lead to more intracellular uptake of drug, inducing the higher apoptosis ratio of cells than free 5-Fu.

  11. Conjugated Linoleic Acids Mediate Insulin Release through Islet G Protein-coupled Receptor FFA1/GPR40*

    Science.gov (United States)

    Schmidt, Johannes; Liebscher, Kathrin; Merten, Nicole; Grundmann, Manuel; Mielenz, Manfred; Sauerwein, Helga; Christiansen, Elisabeth; Due-Hansen, Maria E.; Ulven, Trond; Ullrich, Susanne; Gomeza, Jesús; Drewke, Christel; Kostenis, Evi

    2011-01-01

    Among dietary components, conjugated linoleic acids (CLAs) have attracted considerable attention as weight loss supplements in the Western world because they reduce fat stores and increase muscle mass. However, a number of adverse effects are also ascribed to the intake of CLAs such as aggravation of insulin resistance and the risk of developing diabetes. However, the mechanisms accounting for the effects of CLAs on glucose homeostasis are incompletely understood. Herein we provide evidence that CLAs specifically activate the cell surface receptor FFA1, an emerging therapeutic target to treat type 2 diabetes. Using different recombinant cellular systems engineered to stably express FFA1 and a set of diverse functional assays including the novel, label-free non-invasive dynamic mass redistribution technology (Corning® Epic® biosensor), both CLA isomers cis-9, trans-11-CLA and trans-10, cis-12-CLA were found to activate FFA1 in vitro at concentrations sufficient to also account for FFA1 activation in vivo. Each CLA isomer markedly increased glucose-stimulated insulin secretion in insulin-producing INS-1E cells that endogenously express FFA1 and in primary pancreatic β-cells of wild type but not FFA1−/− knock-out mice. Our findings establish a clear mechanistic link between CLAs and insulin production and identify the cell surface receptor FFA1 as a molecular target for CLAs, explaining their acute stimulatory effects on insulin secretion in vivo. CLAs are also revealed as insulinotropic components in widely used nutraceuticals, a finding with significant implication for development of FFA1 modulators to treat type 2 diabetes. PMID:21339298

  12. Conjugated linoleic acid (CLA) promotes endurance capacity via peroxisome proliferator-activated receptor δ-mediated mechanism in mice.

    Science.gov (United States)

    Kim, Yoo; Kim, Daeyoung; Park, Yeonhwa

    2016-12-01

    Previously, it was reported that conjugated linoleic acid (CLA) with exercise training potentially improved endurance capacity via the peroxisome proliferator-activated receptor δ (PPARδ)-mediated mechanism in mice. This study determined the role of exercise and/or CLA in endurance capacity and PPARδ-associated regulators. Male 129Sv/J mice were fed either control (soybean oil) or CLA (0.5%) containing diets for 4 weeks and were further divided into sedentary or training regimes. CLA supplementation significantly reduced body weight and fat mass independent of exercise during the experimental period. Endurance capacity was significantly improved by CLA supplementation, while no effect of exercise was observed. Similarly, CLA treatment significantly increased expressions of sirtuin 1 and PPARγ coactivator-1α, up-stream regulators of PPARδ, in both sedentary and trained animals. With respect to downstream markers of PPARδ, CLA up-regulated the key biomarker needed to stimulate mitochondrial biogenesis, nuclear respiratory factor 1. Moreover, CLA supplementation significantly induced overall genes associated with muscle fibers, such as type I (slow-twitch) and type II (fast twitch). Taken together, it suggests that CLA improves endurance capacity independent of mild-intensity exercise via PPARδ-mediated mechanism.

  13. Conjugated linoleic acid induces apoptosis through estrogen receptor alpha in human breast tissue

    Directory of Open Access Journals (Sweden)

    Liu Suling

    2008-07-01

    Full Text Available Abstract Background Conjugated linoleic acid (CLA, a naturally occurring fatty acid found in ruminant products such as milk and beef, has been shown to possess anti-cancer activities in in vivo animal models and in vitro cell culture systems. In human breast cancer, the overall duration of estrogen exposure is the most important risk factor for developing estrogen-responsive breast cancer. Accordingly, it has been suggested that estrogen exposure reduces apoptosis through the up-regulation of the anti-apoptosis protein, Bcl-2. Bcl-2, an anti-apoptotic protein, regulates apoptosis and plays a crucial role in the development and growth regulation of normal and cancerous cells. Our research interest is to examine the effects of CLA on the induction of apoptosis in human breast tissues. Methods The localization of Bcl-2 in both normal and cancerous human breast tissues was determined by immunohistochemical staining and the Bcl-2 protein expression was tested by western blot analysis. Co-culture of epithelial cells and stromal cells was carried out in the presence or absence of CLA to evaluate apoptosis in the context of a cell-cell interaction. Results The results showed that both normal and cancerous breast tissues were positive for Bcl-2 staining, which was higher overall in mammary ducts but very low in the surrounding stromal compartment. Interestingly, by quantifying the western blot data, basal Bcl-2 protein levels were higher in normal breast epithelial cells than in cancerous epithelial cells. Furthermore, treatment with 17β-estradiol (E2 stimulated growth and up-regulated Bcl-2 expression in estrogen responsive breast epithelial cells; however, these carcinogenic effects were diminished by either CLA or 4-Hydroxytamoxifen (Tam and were suppressed further by the combination of CLA and Tam. In both one cell type cultured and co-culture systems, CLA induced cell apoptosis in ERα transfected MDA-MB-231 cells but not in the wild type MDA

  14. Design, synthesis, cytocidal activity and estrogen receptor α affinity of doxorubicin conjugates at 16α-position of estrogen for site-specific treatment of estrogen receptor positive breast cancer.

    Science.gov (United States)

    Saha, Pijus; Fortin, Sébastien; Leblanc, Valérie; Parent, Sophie; Asselin, Éric; Bérubé, Gervais

    2012-09-01

    Doxorubicin (DOX) is an important medicine for the treatment of breast cancer, which is the most frequently diagnosed and the most lethal cancer in women worldwide. However, the clinical use of DOX is impeded by serious toxic effects such as cardiomyopathy and congestive heart failure. Covalently linking DOX to estrogen to selectively deliver the drug to estrogen receptor-positive (ER(+)) cancer tissues is one of the strategies under investigation for improving the efficacy and decreasing the cardiac toxicity of DOX. However, conjugation of drug performed until now was at 3- or 17-position of estrogen, which is not ideal since the hydroxyl groups at this position are important for receptor binding affinity. In this study, we designed, prepared and evaluated in vitro the first estrogen-doxorubicin conjugates at 16α-position of estradiol termed E-DOXs (8a-d). DOX was conjugated using a 3-9 carbon atoms alkylamide linking arm. E-DOXs were prepared from estrone using a seven-step procedure to afford the desired conjugates in low to moderate yields. The antiproliferative activities of the E-DOX 8a conjugate through a 3-carbon spacer chain on ER(+) MCF7 and HT-29 are in the micromolar range while inactive on M21 and the ER(-) MDA-MB-231 cells (>50 μM). Compound 8a exhibits a selectivity ratio (ER(+)/ER(-) cell lines) of >3.5. Compounds 8b-8d bearing alkylamide linking arms ranging from 5 to 9 carbon atoms were inactive at the concentrations tested (>50 μM). Interestingly, compounds 8a-8c exhibited affinity for the estrogen receptor α (ERα) in the nanomolar range (72-100 nM) whereas compound 8d exhibited no affinity at concentrations up to 215 nM. These results indicate that a short alkylamide spacer is required to maintain both antiproliferative activity toward ER(+) MCF7 and affinity for the ERα of the E-DOX conjugates. Compound 8a is potentially a promising conjugate to target ER(+) breast cancer and might be useful also for the design of more potent E

  15. Binding of estrogen receptor with estrogen conjugated to bovine serum albumin (BSA).

    Science.gov (United States)

    Taguchi, Yasuto; Koslowski, Mirek; Bodenner, Donald L

    2004-08-19

    BACKGROUND: The classic model of estrogen action requires that the estrogen receptor (ER) activates gene expression by binding directly or indirectly to DNA. Recent studies, however, strongly suggest that ER can act through nongenomic signal transduction pathways and may be mediated by a membrane bound form of the ER. Estradiol covalently linked to membrane impermeable BSA (E2-BSA) has been widely used as an agent to study these novel membrane-associated ER events. However, a recent report suggests that E2-BSA does not compete for E2 binding to purified ER in vitro. To resolve this apparent discrepancy, we performed competition studies examining the binding of E2 and E2-BSA to both purified ER preparations and ER within intact cells. To eliminate potential artifacts due to contamination of commercially available E2-BSA preparations with unconjugated E2 (usually between 3-5%), the latter was carefully removed by ultrafiltration. RESULTS: As previously reported, a 10-to 1000-fold molar excess of E2-BSA was unable to compete with 3H-E2 binding to ER when added simultaneously. However, when ER was pre-incubated with the same concentrations of E2-BSA, the binding of 3H-E2 was significantly reduced. E2-BSA binding to a putative membrane-associated ER was directly visualized using fluorescein labeled E2-BSA (E2-BSA-FITC). Staining was restricted to the cell membrane when E2-BSA-FITC was incubated with stable transfectants of the murine ERalpha within ER-negative HeLa cells and with MC7 cells that endogenously produce ERalpha. This staining appeared highly specific since it was competed by pre-incubation with E2 in a dose dependent manner and with the competitor ICI-182,780. CONCLUSIONS: These results demonstrate that E2-BSA does bind to purified ER in vitro and to ER in intact cells. It seems likely that the size and structure of E2-BSA requires more energy for it to bind to the ER and consequently binds more slowly than E2. More importantly, these findings demonstrate

  16. Nuclear estrogen receptor targeted photodynamic therapy: selective uptake and killing of MCF-7 breast cancer cells by a C17alpha-alkynylestradiol-porphyrin conjugate.

    Science.gov (United States)

    Swamy, Narasimha; Purohit, Ajay; Fernandez-Gacio, Ana; Jones, Graham B; Ray, Rahul

    2006-10-15

    We hypothesized that over-expression of estrogen receptor (ER) in hormone-sensitive breast cancer could be harnessed synergistically with the tumor-migrating effect of porphyrins to selectively deliver estrogen-porphyrin conjugates into breast tumor cells, and preferentially kill the tumor cells upon exposure to red light. In the present work we synthesized four (4) conjugates of C17-alpha-alkynylestradiol and chlorin e6-dimethyl ester with varying tether lengths, and showed that all these conjugates specifically bound to recombinant ER alpha. In a cellular uptake assay with ER-positive MCF-7 and ER-negative MDA-MB 231 human breast cancer cell-lines, we observed that one such conjugate (E17-POR, XIV) was selectively taken up in a dose-dependent and saturable manner by MCF-7 cells, but not by MDA-MB 231 cells. Furthermore, MCF-7 cells, but not MDA-MB 231 cells, were selectively and efficiently killed by exposure to red light after incubation with E17-POR. Therefore, the combination approach, including drug and process modalities has the potential to be applied clinically for hormone-sensitive cancers in organs where ER is significantly expressed. This could potentially be carried out either as monotherapy involving a photo-induced selective destruction of tumor cells and/or adjuvant therapy in post-surgical treatment for the destruction of residual cancer cells in tissues surrounding the tumor.

  17. In vitro and in vivo imaging of prostate cancer angiogenesis using anti-vascular endothelial growth factor receptor 2 antibody-conjugated quantum dot

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Haejin; Lee, Jiyeon; Song, Rita; Lee, Jung Han [Medicinal Chemistry Laboratory, Institute Pasteur Korea (IP-K), Seongnam (Korea, Republic of); Hwang, Sung Il; Lee, Hak Jong [Seoul National University Bundang Hospital, Institute of Radiation Medicine, Seoul National University Medical Research Center, Clinical Research Institute, Seongnam (Korea, Republic of); Kim, Young Hwa [Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2013-01-15

    Authors aimed to determine the targeting ability of vascular endothelial growth factor receptor 2 (VEGFR2)-conjugated quantum dots (QDs) in vitro, and apply it for a xenograft prostate cancer mouse model. Conjugation reaction of QDs was performed by using the N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) and sulfo-(N-hydroxysulfosuccinimide) (Sulfo-NHS). The human umbilical vein cord endothelial cells (HUVECs) were incubated with QDs, conjugated with antiVGFR2, to see a specific binding in vitro. Fluorescent cell images were taken by a confocal microscope. The human prostate cancer cells (PC3) were injected to five nude mice on hind limbs to make the xenograft tumor model. QD-antiVEGFR2 antibody complex was injected into the tumor model and fluorescence measurements were performed at 1, 4, 9, 12, 15, and 24 hours after the injection. The specific interaction between HUVECs and QD-antiVEGFR2 antibody was clearly shown in vitro. The in vivo fluorescence image disclosed that there was an increased signal of tumor, 12 hours after the injection of QDs. By showing endothelial cells binding with QDs-antiVEGFR2 antibodyand an experimental application of the antibody for VEGFR2 imaging in the prostate cancer xenograft mouse model, we suggests that the antibody-conjugated QDs can be a potential imaging tool for angiogenesis of the cancer.

  18. Glucagon-like Peptide 1 Conjugated to Recombinant Human Serum Albumin Variants with Modified Neonatal Fc Receptor Binding Properties. Impact on Molecular Structure and Half-Life

    DEFF Research Database (Denmark)

    Bukrinski, Jens T.; Sønderby, Pernille; Antunes, Filipa

    2017-01-01

    cells of blood vessels, which rescues circulating HSA from lysosomal degradation. We have conjugated GLP-1 to C34 of native sequence recombinant HSA (rHSA) and two rHSA variants; one with increased and one with decreased binding affinity to hFcRn. We have investigated the impact of conjugation on Fc......Rn binding affinities, GLP-1 potency and pharmacokinetics, combined with the solution structure of the rHSA variants and GLP-1 albumin conjugates. The solution structures, determined by small angle X-ray scattering, show the GLP-1 pointing away from the surface of rHSA. Combining the solution structures...... with the available structural information on the FcRn and GLP-1 receptor (GLP-1R) obtained from X-ray crystallography, we can explain the observed in-vitro and in-vivo behaviour. We conclude that the conjugation of GLP-1 to rHSA does not affect the interaction between rHSA and FcRn, while the observed decrease...

  19. Targeting urokinase and the transferrin receptor with novel, anti-mitotic N-alkylisatin cytotoxin conjugates causes selective cancer cell death and reduces tumor growth.

    Science.gov (United States)

    Vine, K L; Indira Chandran, V; Locke, J M; Matesic, L; Lee, J; Skropeta, D; Bremner, J B; Ranson, M

    2012-01-01

    Tumor-specific delivery of ligand-directed prodrugs can increase the therapeutic window of chemotherapeutics by maintaining efficacy whilst decreasing toxic side effects. We have previously described a series of synthetic N-alkylated isatin cytotoxins that destabilize microtubules and induce apoptosis with 10-fold greater potency than conventional anti-mitotics in vitro. Here, we report the characterization, in vitro cytotoxicity and in vivo efficacy of a lead compound, 5,7-dibromo-N-(p-hydroxymethylbenzyl)isatin (N-AI) conjugated via an esterase-labile linker (N-AIE) to two proven targeting ligands, transferrin (Tf) and plasminogen activator inhibitor type 2 (PAI-2/serpinB2). N-AI was released from N-AIE and the targeting ligands Tf/PAI-2 in an esterase-dependent manner at 37 C and both Tf- and PAI-2-N-AIE conjugates were stable at physiological pH. Human cancer cell lines which vary in their expression levels of Tf receptor (TfR/CD71) and PAI-2 target, receptor bound urokinase (uPA) selectively internalized the conjugates. Tf-N-AIE was up to 24 times more active than the free drug and showed clear selectivity patterns based on TfR levels. PAI-2-N-AIE showed equivalent activity compared to the parent drug and strong selectivity patterns for uPA levels. In preliminary in vivo experiments, the PAI-2- and Tf-N-AIE conjugates were efficacious at 1/20(th) and 1/10(th) of the dose of the free N-AI, respectively, in a metastatic, orthotopic human breast tumor xenograft mouse model. Thus, this strategy specifically delivers and concentrates a novel class of isatin-based, tubulin destabilizing agents to tumors in vivo and warrants further detailed preclinical investigation.

  20. Elimination of Tumor Cells Using Folate Receptor Targeting by Antibody-Conjugated, Gold-Coated Magnetite Nanoparticles in a Murine Breast Cancer Model

    Directory of Open Access Journals (Sweden)

    Evan S. Krystofiak

    2012-01-01

    Full Text Available Background. The chemotherapeutic treatment of cancer suffers from poor specificity for targeting the tumor cells and often results in adverse effects such as systemic toxicity, damage to nontarget tissues, and development of drug-resistant tumors in patients. Increasingly, drug nanocarriers have been explored as a way of lessening or overcoming these problems. In this study, antibody-conjugated Au-coated magnetite nanoparticles, in conjunction with inductive heating produced by exposure to an oscillating magnetic field (OMF, were evaluated for their effects on the viability of tumor cells in a murine model of breast cancer. Treatment effects were evaluated by light microscopy and SEM. Results. 4T1 mammary epithelial carcinoma cells overexpressing the folate receptor were targeted with an anti-folate receptor primary antibody, followed by labeling with secondary antibody-conjugated Au-coated magnetite nanoparticles. In the absence of OMF exposure, nanoparticle labeling had no effect on 4T1 cell viability. However, following OMF treatment, many of the labeled 4T1 cells showed extensive membrane damage by SEM analysis, and dramatically reduced viability as assessed using a live/dead staining assay. Conclusions. These results demonstrate that Au-coated magnetite targeted to tumor cells through binding to an overexpressed surface receptor, in the presence of an OMF, can lead to tumor cell death.

  1. Pharmacokinetics and pharmacodynamics of a polyethylene glycol (PEG)-conjugated GLP-receptor agonist once weekly in Chinese patients with type 2 diabetes.

    Science.gov (United States)

    Yang, Guang-Ran; Zhao, Xiu-Li; Jin, Fan; Shi, Li-Hong; Yang, Jin-Kui

    2015-02-01

    This multi-center, randomized, double-blind, multiple dose-escalation study was conducted to assess the pharmacokinetics and pharmacodynamics of a newly developed polyethylene glycol (PEG)-conjugated glucagon-like peptide-1 (GLP-1) receptor agonist, PEX168 once weekly in Chinese patients with type 2 diabetes (T2DM). Fifty patients aged 20-65 years, either treatment-naive or having been treated with single oral antidiabetic agents were eligible. Antidiabetic agents were stopped for 14 days before the study was initiated. Patients were allocated randomly into groups with subcutaneous PEX168 or placebo once-weekly for 8 weeks followed by 6 weeks observation. From baseline to 8 weeks, HbA1c were decreased by up to 0.0, 0.2, 0.6, 0.9, and -0.4% in the 50, 100, 200, 300 μg PEX168 groups, and placebo group respectively. The mean elimination half-life of PEX168 was 131.8-139.8 hours. The mean tmax was 67.3 hours. Steady-state plasma PEX168 concentrations were attained after 4 weeks. PEX168 once-weekly were tolerable by the patients: adverse effects reported ranged from 'mild' to 'moderate'. The most frequent drug-related adverse effects were nausea, vomiting, and diarrhea of mild to moderate severity. Administration of the PEG-conjugated GLP-1 receptor agonist PEX168 resulted in dose-proportional pharmacokinetic and antidiabetic pharmacodynamic activity.

  2. Anti-PDGF receptor β antibody-conjugated squarticles loaded with minoxidil for alopecia treatment by targeting hair follicles and dermal papilla cells.

    Science.gov (United States)

    Aljuffali, Ibrahim A; Pan, Tai-Long; Sung, Calvin T; Chang, Shu-Hao; Fang, Jia-You

    2015-08-01

    This study developed lipid nanocarriers, called squarticles, conjugated with anti-platelet-derived growth factor (PDGF)-receptor β antibody to determine whether targeted Minoxidil (MXD) delivery to the follicles and dermal papilla cells (DPCs) could be achieved. Squalene and hexadecyl palmitate (HP) were used as the matrix of the squarticles. The PDGF-squarticles showed a mean diameter and zeta potential of 195 nm and -46 mV, respectively. Nanoparticle encapsulation enhanced MXD porcine skin deposition from 0.11 to 0.23 μg/mg. The antibody-conjugated nanoparticles ameliorated follicular uptake of MXD by 3-fold compared to that of the control solution in the in vivo mouse model. Both vertical and horizontal skin sections exhibited a wide distribution of nanoparticles in the follicles, epidermis, and deeper skin strata. The encapsulated MXD moderately elicited proliferation of DPCs and vascular endothelial growth factor (VEGF) expression. The active targeting of PDGF-squarticles may be advantageous to improving the limited success of alopecia therapy. Topical use of minoxidil is only one of the very few treatment options for alopecia. Nonetheless, the current delivery method is far from ideal. In this article, the authors developed lipid nanocarriers with anti-platelet-derived growth factor receptor ? antibody to target dermal papilla cells, and showed enhanced uptake of minoxidil. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. High affinity receptor labeling based on basic leucine zipper domain peptides conjugated with pH-sensitive fluorescent dye: Visualization of AMPA-type glutamate receptor endocytosis in living neurons.

    Science.gov (United States)

    Hayashi, Ayako; Asanuma, Daisuke; Kamiya, Mako; Urano, Yasuteru; Okabe, Shigeo

    2016-01-01

    Techniques to visualize receptor trafficking in living neurons are important, but currently available methods are limited in their labeling efficiency, specificity and reliability. Here we report a method for receptor labeling with a basic leucine zipper domain peptide (ZIP) and a binding cassette specific to ZIP. Receptors are tagged with a ZIP-binding cassette at their extracellular domain. Tagged receptors expressed in cultured cells were labeled with exogenously applied fluorescently labeled ZIP with low background and high affinity. To test if ZIP labeling is useful in monitoring endocytosis and intracellular trafficking, we next conjugated ZIP with a pH-sensitive dye RhP-M (ZIP-RhP-M). ZIP binding to its binding cassette was pH-resistant and RhP-M fluorescence dramatically increased in acidic environment. Thus AMPA-type glutamate receptors (AMPARs) labeled by ZIP-RhP-M can report receptor endocytosis and subsequent intracellular trafficking. Application of ZIP-RhP-M to cultured hippocampal neurons expressing AMPARs tagged with a ZIP-binding cassette resulted in appearance of fluorescent puncta in PSD-95-positive large spines, suggesting local endocytosis and acidification of AMPARs in individual mature spines. This spine pool of AMPARs in acidic environment was distinct from the early endosomes labeled by transferrin uptake. These results suggest that receptor labeling by ZIP-RhP-M is a useful technique for monitoring endocytosis and intracellular trafficking. This article is part of the Special Issue entitled 'Synaptopathy--from Biology to Therapy'.

  4. The collagen receptor uPARAP/Endo180 as a novel target for antibody-drug conjugate mediated treatment of mesenchymal and leukemic cancers

    DEFF Research Database (Denmark)

    Nielsen, Christoffer Fagernæs; van Putten, Sander Maarten; Lund, Ida Katrine

    2017-01-01

    A key task in developing the field of personalized cancer therapy is the identification of novel molecular targets that enable treatment of cancers not susceptible to other means of specific therapy. The collagen receptor uPARAP/Endo180 is overexpressed by malignant cells in several non-epithelia......A key task in developing the field of personalized cancer therapy is the identification of novel molecular targets that enable treatment of cancers not susceptible to other means of specific therapy. The collagen receptor uPARAP/Endo180 is overexpressed by malignant cells in several non......-epithelial cancers, notably including sarcomas, glioblastomas and subsets of acute myeloid leukemia. In contrast, in healthy adult individuals, expression is restricted to minor subsets of mesenchymal cells. Functionally, uPARAP/Endo180 is a rapidly recycling endocytic receptor that delivers its cargo directly...... into the endosomal-lysosomal system, thus opening a potential route of entry into receptor-positive cells. This combination of specific expression and endocytic function appears well suited for targeting of uPARAP/Endo180-positive cancers by antibody-drug conjugate (ADC) mediated drug delivery. Therefore, we...

  5. Conjugated Linoleic Acids Mediate Insulin Release through Islet G Protein-coupled Receptor FFA1/GPR40

    DEFF Research Database (Denmark)

    Schmidt, Johannes; Liebscher, Kathrin; Merten, Nicole

    2011-01-01

    Among dietary components, conjugated linoleic acids (CLAs) have attracted considerable attention as weight loss supplements in the Western world because they reduce fat stores and increase muscle mass. However, a number of adverse effects are also ascribed to the intake of CLAs such as aggravatio...... in widely used nutraceuticals, a finding with significant implication for development of FFA1 modulators to treat type 2 diabetes....

  6. Concise site-specific synthesis of DTPA-peptide conjugates: application to imaging probes for the chemokine receptor CXCR4.

    Science.gov (United States)

    Masuda, Ryo; Oishi, Shinya; Ohno, Hiroaki; Kimura, Hiroyuki; Saji, Hideo; Fujii, Nobutaka

    2011-05-15

    Diethylenetriaminepentaacetic acid (DTPA) is a useful chelating agent for radionuclides such as (68)Ga, (99m)Tc and (111)In, which are applicable to nuclear medicine imaging. In this study, we established a facile synthetic protocol for the production of mono-DTPA-conjugated peptide probes. A novel monoreactive DTPA precursor reagent was synthesized in two steps using the chemistry of the o-nitrobenzenesulfonyl (Ns) protecting group, and under mild conditions this DTPA precursor was incorporated onto an N(ε)-bromoacetylated Lys of a protected peptide resin. The site-specific DTPA conjugation was facilitated by using a highly acid-labile 4-methyltrityl (Mtt) protecting group for the target site of the bioactive peptide during the solid-phase synthesis. A combination of both techniques yielded peptides with disulfide bonds, such as octreotide and polyphemusin II-derived CXCR4 antagonists. DTPA-peptide conjugates were purified in a single step following cleavage from the resin and disulfide bond formation. This site-specific on-resin construction strategy was used for the design and synthesis of a novel In-DTPA-labeled CXCR4 antagonist, which exhibited highly potent inhibitory activity against SDF-1-CXCR4 binding. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Investigation of folate-conjugated fluorescent silica nanoparticles for targeting delivery to folate receptor-positive tumors and their internalization mechanism

    Directory of Open Access Journals (Sweden)

    Yang H

    2011-09-01

    Full Text Available Hong Yang1,*, Changchun Lou1,*, Mingming Xu1, Chunhui Wu1, Hirokazu Miyoshi2, Yiyao Liu1,31Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China; 2Radioisotope Research Center, University of Tokushima, Tokushima, Japan; 3Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing, People’s Republic of China *These authors contributed equally to this work Abstract: Multifunctionalized nanoparticles (NPs are emerging as ideal tools for gene/drug delivery, bioimaging, labeling, or intracellular tracking in biomedical applications, and have attracted considerable attention owing to their unique advantages. In this study, fluorescent silica NPs were synthesized by a modified Stöber method using conjugates of 3- mercaptopropyltrimethoxysilane (MPS and maleimide-fluorescein isothiocyanate (maleimide-FITC. Mean diameters of the NPs were controlled between 212–2111 nm by regulating MPS concentration in the reaction mixture. Maleimide-FITC molecules were doped into NPs or conjugated to the surface of NPs through the chemical reaction of maleimide and thiol groups. The data showed that the former NPs are better than the latter by comparing their fluorescence intensity. Furthermore, folate molecules were linked to the FITC-doped silica NPs by using polyethylene glycol (PEG (NH2-PEG-maleimide as a spacer, thus forming folate receptor targeting fluorescent NPs, referred to as NPs(FITC-PEG-Folate. The quantitative analysis of cellular internalization into different cancer cells showed that the delivery efficiency of KB cells (folate receptor-positive cells is more than six-fold higher than that of A549 cells (folate receptor-negative cells. The delivery efficiency of KB cells decreased significantly after free folate addition to the cell culture medium because the

  8. Site-selective conjugation of an anticoagulant aptamer to recombinant albumins and maintenance of neonatal Fc receptor binding

    DEFF Research Database (Denmark)

    Schmøkel, Julie; Voldum, Anders; Tsakiridou, Georgia

    2017-01-01

    Aptamers are an attractive molecular medicine that offers high target specificity. Nucleic acid-based aptamers, however, are prone to nuclease degradation and rapid renal excretion that require blood circulatory half-life extension enabling technologies. The long circulatory half...... of a factor IXa anticoagulant aptamer on aptamer functionality and human FcRn (hFcRn) engagement using recombinant human albumin (rHA) of either a wild type (WT) or an engineered human FcRn high binding variant (HB). Albumin-aptamer conjugates, connected covalently through a heterobifunctional succinimidyl 4......-(N-maleimidomethyl)cyclohexane-1-carboxylate linker, were successfully prepared and purified by high performance liquid chromatography as confirmed by gel electrophoresis band-shift analysis and matrix-assisted laser desorption/ionization time of flight. Minimal reduction (∼25%) in activity of WT...

  9. A Glu-urea-Lys Ligand-conjugated Lipid Nanoparticle/siRNA System Inhibits Androgen Receptor Expression In Vivo

    Science.gov (United States)

    Lee, Justin B; Zhang, Kaixin; Tam, Yuen Yi C; Quick, Joslyn; Tam, Ying K; Lin, Paulo JC; Chen, Sam; Liu, Yan; Nair, Jayaprakash K; Zlatev, Ivan; Rajeev, Kallanthottathil G; Manoharan, Muthiah; Rennie, Paul S; Cullis, Pieter R

    2016-01-01

    The androgen receptor plays a critical role in the progression of prostate cancer. Here, we describe targeting the prostate-specific membrane antigen using a lipid nanoparticle formulation containing small interfering RNA designed to silence expression of the messenger RNA encoding the androgen receptor. Specifically, a Glu-urea-Lys PSMA-targeting ligand was incorporated into the lipid nanoparticle system formulated with a long alkyl chain polyethylene glycol-lipid to enhance accumulation at tumor sites and facilitate intracellular uptake into tumor cells following systemic administration. Through these features, and by using a structurally refined cationic lipid and an optimized small interfering RNA payload, a lipid nanoparticle system with improved potency and significant therapeutic potential against prostate cancer and potentially other solid tumors was developed. Decreases in serum prostate-specific antigen, tumor cellular proliferation, and androgen receptor levels were observed in a mouse xenograft model following intravenous injection. These results support the potential clinical utility of a prostate-specific membrane antigen–targeted lipid nanoparticle system to silence the androgen receptor in advanced prostate cancer.

  10. Receptor-targeted cytotoxic peptide-drug conjugates%受体靶向多肽载体抗肿瘤药物

    Institute of Scientific and Technical Information of China (English)

    孙立春; Coy DH

    2015-01-01

    常规化疗药物对癌细胞没有选择性,常常会导致严重的副作用。提高这些药物的靶向特异性已成为药物开发的热点方向之一。一些小分子多肽能够靶向作用于特定的受体,因而被用作癌症化疗药物的载体。化疗药物与多肽载体偶联构成新的多肽载体抗肿瘤药物。这些药物具有高特异性、高亲和力和肿瘤渗透力等优点,能够通过细胞表面的特定受体将药物送到靶向癌细胞内,提高抗癌效果、减少副作用和癌细胞的耐药性。多肽载体靶向药物被誉为新一代的靶向特异性的抗肿瘤药物之一。%Conventional cancer chemotherapy has very limited effects due to lacking speciifcity resulting in severe toxic side effects. Certain G protein-coupled receptors (GPCRs) are highly expressed in many tumor cells and tumoral blood veins, with their cognate ligands being peptides. Therefore, these peptides, especially their long-acting analogs, can be applied as drug-delivery vehicles by coupling with cytotoxic agents. These novel cytotoxic peptide-drug conjugates display more potent anti-tumor efifcacy by targeting the cognate receptors while reducing toxic side effects and overcoming multiple drug resistance. This new receptor-targeted approach may provide a promising opportunity for the improvement of cancer treatments.

  11. [The influence of immunization of rats with BSA-conjugated peptide 269-280 of type 3 melanocortin receptor on the metabolic parameters and thyroid functions].

    Science.gov (United States)

    Derkach, K V; Shpakova, E A; Zharova, O A; Bondareva, V M; Shpakov, A O

    2014-01-01

    One of the approaches to study the role of the brain hormonal signaling systems in the regulation of biochemical and physiological processes is their shutdown using the antibodies generated to peptides corresponding to extracellular regions of receptors. The brain type 3 melanocortin receptors (M3R) play an important role in the central regulation of the metabolism and the endocrine system. However, the influence of prolonged inhibition of M3R on energy metabolism, insulin resistance, and thyroid gland (TG) function is practically not studied. The aim of the study was to investigate the influence of prolonged repeated immunization of male rats with the BSA-conjugated peptide Ala-[Pro-Thr-Asn-Pro-Tyr-Cys-Ile-Cys-Thr-Thr-Ala-His269-280]-Ala (A[269- 280]A) corresponding to the third extracellular loop of M3R on their metabolic parameters and functional activity of TG. 9 months after the first immunization, the weight of rats was reduced and after 12-13 months was significantly lower than in controls. The weight of abdominal and brown adipose tissues, on the contrary, increased. At the same timeline there was an increase in the fasting glucose and insulin levels, and increase of the HOMA-IR index (by 75%) indicating that immunized animals develop insulin resistance. The rats have increased glucose utilization due to an increase of insulin production by pancreatic β-cells. 12 months after the first immunization, the increase of the triglycerides level (by 74%) and the ratio of LDL- and HDL-cholesterol (by 36%) were revealed. 13 months after the start of immunization, the levels of free and total thyroxine and total triiodothyronine significantly decreased. In the TG plasma membranes of immunized rats the weakening adenylyl cyclase stimulating effect of thyroid-stimulating hormone was detected. Thus, long-term decrease in the bra- in M3R activity due to repeated immunization of rats with BSA-conjugated peptide A[269-280]A induces the disturbances of the peripheral

  12. Folic acid-conjugated GdPO4:Tb3+@SiO2 Nanoprobe for folate receptor-targeted optical and magnetic resonance bi-modal imaging

    Science.gov (United States)

    Xu, Xianzhu; Zhang, Xiaoying; Wu, Yanli

    2016-11-01

    Both fluorescent and magnetic nanoprobes have great potential applications for diagnostics and therapy. In the present work, a folic acid-conjugated and silica-modified GdPO4:Tb3+ (GdPO4:Tb3+@SiO2-FA) dual nanoprobe was strategically designed and synthesized for the targeted dual-modality optical and magnetic resonance (MR) imaging via a facile aqueous method. Their structural, optical, and magnetic properties were determined using transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR), ultraviolet-visible spectra (UV-Vis), photoluminescence (PL), and superconducting quantum interference device (SQUID). These results indicated that GdPO4:Tb3+@SiO2-FA were uniform monodisperse core-shell structured nanorods (NRs) with an average length of 200 nm and an average width of 25 nm. The paramagnetic property of the synthesized GdPO4:Tb3+@SiO2-FA NRs was confirmed with its linear hysteresis plot (M-H). In addition, the NRs displayed an obvious T1-weighted effect and thus it could potentially serve as a T1-positive contrast agent. The NRs emitted green lights due to the 5D4 → 7F5 transition of the Tb3+. The in vitro assays with NCI-H460 lung cancer cells and human embryonic kidney cell line 293T cells indicated that the GdPO4:Tb3+@SiO2-FA nanoprobe could specifically bind the cells bearing folate receptors (FR). The MTT assay of the NRs revealed that its cytotoxicity was very low. Further in vivo MRI experiments distinctively depict enhanced anatomical features in a xenograft tumor. These results suggest that the GdPO4:Tb3+@SiO2-FA NPs have excellent imaging and cell-targeting abilities for the folate receptor-targeted dual-modality optical and MR imaging and can be potentially used as the nanoprobe for bioimaging.

  13. MAPK pathway inhibition enhances the efficacy of an anti-endothelin B receptor drug conjugate by inducing target expression in melanoma.

    Science.gov (United States)

    Asundi, Jyoti; Lacap, Jennifer A; Clark, Suzanna; Nannini, Michelle; Roth, Leslie; Polakis, Paul

    2014-06-01

    Therapies targeting the mitogen-activated protein (MAP) kinase pathway in melanoma have produced significant clinical responses; however, duration of response is limited by acquisition of drug resistance. Rational drug combinations may improve outcomes in this setting. We assessed the therapeutic combination of an antibody-drug conjugate (ADC) targeting the endothelin B receptor (EDNRB) with small-molecule inhibitors of the MAP kinase signaling pathway in melanoma. Cell lines and tumor models containing either mutant BRAF or NRAS, or wild-type for both, were exposed to small-molecule inhibitors of BRAF and MEK. Expression of EDNRB was analyzed and the therapeutic impact of combining the anti-EDNRB ADC with the BRAF and MEK inhibitors was assessed. Increased expression of EDNRB in response to inhibition of BRAF and/or MEK was observed and augmented the antitumor activity of the ADC. Enhanced target expression and ADC antitumor activity were realized irrespective of the response of the tumor model to the BRAF or MEK inhibitors alone and could be achieved in melanoma with mutant NRAS, BRAF, or neither mutation. Cells that acquired resistance to BRAF inhibition through long-term culture retained drug-induced elevated levels of EDNRB expression. Expression of EDNRB was not enhanced in normal human melanocytes by inhibition of BRAF and the combination of the ADC with MAPK inhibitors was well-tolerated in mice. The anti-EDNRB ADC combines well with BRAF and MEK inhibitors and could have therapeutic use in the majority of human melanoma cases.

  14. Upregulation of peroxisome proliferator-activated receptors and liver fatty acid binding protein in hepatic cells of broiler chicken supplemented with conjugated linoleic acids

    Directory of Open Access Journals (Sweden)

    Suriya Kumari Ramiah

    2015-09-01

    Full Text Available Since conjugated linoleic acid (CLA has structural and physiological characteristics similar to peroxisome proliferators, it is hypothesized that CLA would upregulate peroxisome proliferator-activated receptor (PPAR and liver fatty acid binding protein (LFABP in the liver of broiler chicken. The aim of the present study was to determine fatty acid composition of liver in CLA-fed broiler chickens and the genes associated with hepatic lipid metabolism. A total of 180-day-old broiler chicks were randomly assigned to two diets containing 0 and 2.5% CLA and fed for 6 weeks. Fatty acid (FA composition of liver and PPAR α and γ and L-FABP were analyzed. It has been demonstrated that CLA was found in the liver of CLA-feed chicken compared to control group. Hepatic PPAR α and γ mRNA levels were upregulated 1.2 and 3-fold in CLA-fed chickens compared to chickens fed diet without CLA respectively. A similar response of upregulation was observed for L-FABP mRNA expression. Our data highlights the role of PPARs as a core regulator in the regulation of lipid metabolism in chicken liver.

  15. Synthesis and purification of a toxin-linked conjugate targeting epidermal growth factor receptor in Escherichia coli.

    Science.gov (United States)

    Ma, Chengyuan; Li, Yang; Li, Zhixin; Huang, Haiyan; Xu, Kan; Xu, Haiyang; Bai, Jieying; Li, Xiao; Zhao, Gang

    2012-05-01

    Aberrant epidermal growth factor receptor (EGFR) signaling is a common feature of multiple tumor types, including glioblastoma (GBM). As such, EGFR has emerged as an attractive target for antitumor therapy. In the present study, we sought to develop an immunotoxin capable of specifically targeting EGFR-expressing cells and mediating inhibition of cell growth and cell killing. The Luffin P1 (LP1) ribosome inactivating protein was chosen to generate a fusion protein, antiEGFR/LP1, based upon its potent protein synthesis inhibition and small size (5 kDa). LP1 was fused to the C-terminus of an anti-EGFR single-chain antibody (scFv). The recombinant antiEGFR/LP1 protein was expressed in Escherichia coli, and refolded and purified on an immobilized Ni(2+)-affinity chromatography column. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting analysis revealed that antiEGFR/LP1 was sufficiently expressed. Confocal microscopy and flow cytometry demonstrated that antiEGFR/LP1 bound specifically to EGFR-positive cells (U251), as almost no binding to EGFR-negative (Jurkat cells) was observed under identical time and dosage conditions. Finally, the MTT cell viability assay showed that antiEGFR/LP1 elicited obvious cytotoxicity toward EGFR-positive tumor cells. Collectively, these results suggest that antiEGFR/LP1 is biologically active and specific toward EGFR-positive tumor cells and may represent an effective EGFR-targeted cancer therapy.

  16. Biodistribution of ~(99)Tc~m Labelled Dextran Conjugates for Sentinel Lymph Node Detection

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Mannosylated dextran conjugates showed high receptor affinity to the receptors on the surface of macrophages in the lymph node. 99Tcm labelled mannosylated dextran conjugates could be used for sentinel lymph node (SLN) detection. In this paper,

  17. Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody-drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity.

    Science.gov (United States)

    Ogitani, Yusuke; Hagihara, Katsunobu; Oitate, Masataka; Naito, Hiroyuki; Agatsuma, Toshinori

    2016-07-01

    Antibody-drug conjugates deliver anticancer agents selectively and efficiently to tumor tissue and have significant antitumor efficacy with a wide therapeutic window. DS-8201a is a human epidermal growth factor receptor 2 (HER2)-targeting antibody-drug conjugate prepared using a novel linker-payload system with a potent topoisomerase I inhibitor, exatecan derivative (DX-8951 derivative, DXd). It was effective against trastuzumab emtansine (T-DM1)-insensitive patient-derived xenograft models with both high and low HER2 expression. In this study, the bystander killing effect of DS-8201a was evaluated and compared with that of T-DM1. We confirmed that the payload of DS-8201a, DXd (1), was highly membrane-permeable whereas that of T-DM1, Lys-SMCC-DM1, had a low level of permeability. Under a coculture condition of HER2-positive KPL-4 cells and negative MDA-MB-468 cells in vitro, DS-8201a killed both cells, whereas T-DM1 and an antibody-drug conjugate with a low permeable payload, anti-HER2-DXd (2), did not. In vivo evaluation was carried out using mice inoculated with a mixture of HER2-positive NCI-N87 cells and HER2-negative MDA-MB-468-Luc cells by using an in vivo imaging system. In vivo, DS-8201a reduced the luciferase signal of the mice, indicating suppression of the MDA-MB-468-Luc population; however, T-DM1 and anti-HER2-DXd (2) did not. Furthermore, it was confirmed that DS-8201a was not effective against MDA-MB-468-Luc tumors inoculated at the opposite side of the NCI-N87 tumor, suggesting that the bystander killing effect of DS-8201a is observed only in cells neighboring HER2-positive cells, indicating low concern in terms of systemic toxicity. These results indicated that DS-8201a has a potent bystander effect due to a highly membrane-permeable payload and is beneficial in treating tumors with HER2 heterogeneity that are unresponsive to T-DM1. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer

  18. In vitro and in vivo evaluation of Alexa Fluor 680-bombesin[7-14]NH2 peptide conjugate, a high-affinity fluorescent probe with high selectivity for the gastrin-releasing peptide receptor.

    Science.gov (United States)

    Ma, Lixin; Yu, Ping; Veerendra, Bhadrasetty; Rold, Tammy L; Retzloff, Lauren; Prasanphanich, Adam; Sieckman, Gary; Hoffman, Timothy J; Volkert, Wynn A; Smith, Charles J

    2007-01-01

    Gastrin-releasing peptide (GRP) receptors are overexpressed on several types of human cancer cells, including breast, prostate, small cell lung, and pancreatic cancers. Bombesin (BBN), a 14-amino acid peptide that is an analogue of human GRP, binds to GRP receptors with very high affinity and specificity. The aim of this study was to develop a new fluorescent probe based on BBN having high tumor uptake and optimal pharmacokinetics for specific targeting and optical imaging of human breast cancer tissue. In this study, solid-phase peptide synthesis was used to produce H(2)N-glycylglycylglycine-BBN[7-14]NH(2) peptide with the following general sequence: H(2)N-G-G-G-Q-W-A-V-G-H-L-M-(NH(2)). This conjugate was purified by reversed-phase high-performance liquid chromatography and characterized by electrospray-ionization mass spectra. The fluorescent probe Alexa Fluor 680-G-G-G-BBN[7-14]NH(2) conjugate was prepared by reaction of Alexa Fluor 680 succinimidyl ester to H(2)N-G-G-G-BBN[7-14]NH(2) in dimethylformamide (DMF). In vitro competitive binding assays, using (125)I-Tyr(4)-BBN as the radiolabeling gold standard, demonstrated an inhibitory concentration 50% value of 7.7 +/- 1.4 nM in human T-47D breast cancer cells. Confocal fluorescence microscopy images of Alexa Fluor 680-G-G-G-BBN[7-14]NH(2) in human T-47D breast cancer cells indicated specific uptake, internalization, and receptor blocking of the fluorescent bioprobe in vitro. In vivo investigations in SCID mice bearing xenografted T-47D breast cancer lesions demonstrated the ability of this new conjugate to specifically target tumor tissue with high selectivity and affinity.

  19. In Vitro and In Vivo Evaluation of Alexa Fluor 680-Bombesin[7–14]NH2 Peptide Conjugate, a High-Affinity Fluorescent Probe with High Selectivity for the Gastrin-Releasing Peptide Receptor

    Directory of Open Access Journals (Sweden)

    Lixin Ma

    2007-05-01

    Full Text Available Gastrin-releasing peptide (GRP receptors are overexpressed on several types of human cancer cells, including breast, prostate, small cell lung, and pancreatic cancers. Bombesin (BBN, a 14–amino acid peptide that is an analogue of human GRP, binds to GRP receptors with very high affinity and specificity. The aim of this study was to develop a new fluorescent probe based on BBN having high tumor uptake and optimal pharmacokinetics for specific targeting and optical imaging of human breast cancer tissue. In this study, solid-phase peptide synthesis was used to produce H2N-glycylglycylglycine-BBN[7–14]NH2 peptide with the following general sequence: H2N-G-G-G-Q-W-A-V-G-H-L-M-(NH2. This conjugate was purified by reversed-phase high-performance liquid chromatography and characterized by electrospray-ionization mass spectra. The fluorescent probe Alexa Fluor 680-G-G-G-BBN[7–14]NH2 conjugate was prepared by reaction of Alexa Fluor 680 succinimidyl ester to H2N-G-G-G-BBN[7–14]NH2 in dimethylformamide (DMF. In vitro competitive binding assays, using 125I-Tyr4-BBN as the radiolabeling gold standard, demonstrated an inhibitory concentration 50% value of 7.7 ± 1.4 nM in human T-47D breast cancer cells. Confocal fluorescence microscopy images of Alexa Fluor 680-G-G-G-BBN[7–14]NH2 in human T-47D breast cancer cells indicated specific uptake, internalization, and receptor blocking of the fluorescent bioprobe in vitro. In vivo investigations in SCID mice bearing xenografted T-47D breast cancer lesions demonstrated the ability of this new conjugate to specifically target tumor tissue with high selectivity and affinity.

  20. Dual receptor-targeting ⁹⁹mTc-labeled Arg-Gly-Asp-conjugated Alpha-Melanocyte stimulating hormone hybrid peptides for human melanoma imaging.

    Science.gov (United States)

    Xu, Jingli; Yang, Jianquan; Miao, Yubin

    2015-04-01

    The aim of this study was to examine whether the substitution of the Lys linker with the aminooctanoic acid (Aoc) and polyethylene glycol (PEG) linker could substantially decrease the non-specific renal uptake of (99m)Tc-labeled Arg-Gly-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) hybrid peptides. The RGD motif {Arg-Gly-Asp-DTyr-Asp} was coupled to [Cys(3,4,10), D-Phe(7), Arg(11)]α-MSH₃₋₁₃ via the Aoc or PEG₂ linker to generate RGD-Aoc-(Arg(11))CCMSH and RGD-PEG-(Arg(11))CCMSH. The biodistribution results of (99m)Tc-RGD-Aoc-(Arg(11))CCMSH and (99m)Tc-RGD-PEG₂-(Arg(11))CCMSH were examined in M21 human melanoma-xenografted nude mice. The substitution of Lys linker with Aoc and PEG₂ linker significantly reduced the renal uptake of (99m)Tc-RGD-Aoc-(Arg(11))CCMSH and (99m)Tc-RGD-PEG₂-(Arg(11))CCMSH by 58% and 63% at 2h post-injection. The renal uptake of (99m)Tc-RGD-Aoc-(Arg(11))CCMSH and (99m)Tc-RGD-PEG₂-(Arg(11))CCMSH was 27.93 ± 3.98 and 22.01 ± 9.89% ID/g at 2 h post-injection. (99m)Tc-RGD-Aoc-(Arg(11))CCMSH displayed higher tumor uptake than (99m)Tc-RGD-PEG₂-(Arg(11))CCMSH (2.35 ± 0.12 vs. 1.71 ± 0.25% ID/g at 2 h post-injection). The M21 human melanoma lesions could be clearly visualized by SPECT/CT using (99m)Tc-RGD-Aoc-(Arg(11))CCMSH as an imaging probe. The favorable effect of Aoc and PEG₂ linker in reducing the renal uptake provided a new insight into the design of novel dual receptor-targeting radiolabeled peptides. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. ScVEGF-PEG-HBED-CC and scVEGF-PEG-NOTA conjugates: comparison of easy-to-label recombinant proteins for [{sup 68}Ga]PET imaging of VEGF receptors in angiogenic vasculature

    Energy Technology Data Exchange (ETDEWEB)

    Eder, Matthias [German Cancer Research Center (DKFZ), 69120 Heidelberg (Germany)], E-mail: m.eder@dkfz.de; Krivoshein, Arcadius V.; Backer, Marina; Backer, Joseph M. [SibTech, Inc., Brookfield, CT 06804 (United States); Haberkorn, Uwe [Department of Nuclear Medicine, University of Heidelberg, 69120 Heidelberg (Germany); Eisenhut, Michael [German Cancer Research Center (DKFZ), 69120 Heidelberg (Germany)

    2010-05-15

    Introduction: VEGF receptors play a key role in angiogenesis and are important targets for several approved and many experimental drugs. Imaging of VEGF receptor expression in malignant tumors would provide important information, which can influence patient management. The aim of this study was the development of an easy-to-label positron-emitting tracer for imaging VEGF receptors. The tracer is based on engineered single-chain VEGF (scVEGF), expressed with cysteine-containing fusion tag (Cys-tag) for site-specific conjugation of PEGylated bifunctional chelating agents, HBED-CC or NOTA, suitable for labeling with {sup 68}Ga at ambient temperature. Methods: scVEGF-PEG-HBED-CC was synthesized by activating a single carboxyl group of the [Fe(HBED-CC)]{sup -} complex with N-hydroxysuccinimide. Reaction of the activated complex with NH{sub 2}-PEG-maleimide was followed by site-specific conjugation of PEGylated chelator to a thiol group in Cys-tag of scVEGF. The scVEGF-PEG-NOTA conjugate was synthesized using NHS-PEG-maleimide and p-NH{sub 2}-Bn-NOTA. {sup 68}Ga complexation was performed in HEPES buffer (pH 4.2) at room temperature. The functional activity after labeling was tested by radioligand cell binding assays. Biodistribution and PET studies in tumor-bearing mice were performed after 1, 2, 3 and 4 h postinjection. Results: The radiolabeling of scVEGF-PEG-HBED-CC proved more efficient than scVEGF-PEG-NOTA allowing to stop the reaction after 4 min (>97% radiochemical yield). Radioligand cell binding assays performed on HEK-293 cells overexpressing VEGFR-2 revealed no change in the binding properties of {sup 68}Ga-radiolabeled scVEGF relative to other scVEGF-based tracers. Both tracers showed comparable results in biodistribution, such as tumor accumulation and low liver uptake. The tracers were stable in 50% human serum for at least 72 h. Conclusions: The conjugates scVEGF-PEG-HBED-CC and scVEGF-PEG-NOTA revealed comparable in vivo characteristics and allowed easy

  2. Biological evaluation of 99mTc-labeled cyclic glycoprotein IIb/IIIa receptor antagonists in the canine arteriovenous shunt and deep vein thrombosis models: effects of chelators on biological properties of [99mTc]chelator-peptide conjugates.

    Science.gov (United States)

    Barrett, J A; Damphousse, D J; Heminway, S J; Liu, S; Edwards, D S; Looby, R J; Carroll, T R

    1996-01-01

    A series of 99mTc-labeled cyclic glycoprotein IIb/IIIa receptor antagonists, [99mTcO(L1-III)]-, [99mTcO-(L6-III)]-, [99mTcO(L1-V)]-, and [99mTcO(L6-V)]-, were evaluated in a canine arteriovenous (AV) shunt model for their potential use as thrombus imaging agents. The thrombus formed consists of a platelet-rich head and a fibrin-rich tail. All four agents were incorporated into the growing thrombus under both arterial (platelet-rich) and venous (platelet-poor) conditions. The rank order for uptake was [99mTcO(L1-V)]- > [99mTcO(L6-V)]- > [99mTcO(L6-III)]- > [99mTcO(L1-III)]- (arterial range, 5.8-0.47% id/g; venous range, 0.58-0.04% id/g). The uptakes of both [99mTcO(L6-III)]- and [99mTcO-(L1-III)]- under both arterial and venous conditions were not significantly greater than that of [99mTc]-albumin and [125I]fibrinogen. In contrast, the uptakes of both [99mTcO(L1-V)]- and [99mTcO(L6-V)]- were significantly greater than those of [99mTc]albumin and [125I]fibrinogen and comparable to that of [111In]platelets under both arterial and venous conditions. All four [99mTc]chelator-peptide conjugates are cleared faster than the controls with the clearance of the conjugates of peptide III faster than that of the conjugates of peptide V. The differences in incorporation are attributable to the effect of both the cyclic peptide and the chelator. The conjugate [99mTcO(L1-V)]- was also studied using a canine DVT (deep vein thrombosis) model. [99mTcO(L1-V)]- was actively incorporated into the growing thrombus with images clearly detectable within 15 min postinjection. At 2 h postinjection, thrombus/blood and thrombus/muscle ratios [region of interest (ROI)/background] were approximately 7/1 and 10/1, respectively. This clearly demonstrated that the conjugate [99mTcO(L1-V)]- has the potential for rapid diagnosis of thrombolic events occurring under both arterial and venous conditions.

  3. Structure of Peptide Sex Pheromone Receptor PrgX and PrgX/Pheromone Complexes and Regulation of Conjugation in Enterococcus faecalis

    Energy Technology Data Exchange (ETDEWEB)

    Shi,K.; Brown, C.; Gu, Z.; Kozlowicz, B.; Dunny, G.; Ohlendorf, D.; Earhart, C.

    2005-01-01

    Many bacterial activities, including expression of virulence factors, horizontal genetic transfer, and production of antibiotics, are controlled by intercellular signaling using small molecules. To date, understanding of the molecular mechanisms of peptide-mediated cell-cell signaling has been limited by a dearth of published information about the molecular structures of the signaling components. Here, we present the molecular structure of PrgX, a DNA- and peptide-binding protein that regulates expression of the conjugative transfer genes of the Enterococcus faecalis plasmid pCF10 in response to an intercellular peptide pheromone signal. Comparison of the structures of PrgX and the PrgX/pheromone complex suggests that pheromone binding destabilizes PrgX tetramers, opening a 70-bp pCF10 DNA loop required for conjugation repression.

  4. Increment in Drug Loading on an Antibody-Drug Conjugate Increases Its Binding to the Human Neonatal Fc Receptor in Vitro.

    Science.gov (United States)

    Brachet, Guillaume; Respaud, Renaud; Arnoult, Christophe; Henriquet, Corinne; Dhommée, Christine; Viaud-Massuard, Marie-Claude; Heuze-Vourc'h, Nathalie; Joubert, Nicolas; Pugnière, Martine; Gouilleux-Gruart, Valérie

    2016-04-04

    Antibody-drug conjugates, such as brentuximab vedotin (BTXv), are an innovative category of monoclonal antibodies. BTXv is bioconjugated via the chemical reduction of cysteine residues involved in disulfide bonds. Species of BTXv containing zero, two, four, six, or eight vedotin molecules per antibody coexist in the stock solution. We investigated the influence of drug loading on the binding of the antibody to FcRn, a major determinant of antibody pharmacokinetics in humans. We developed a hydrophobic interaction chromatography (HIC) method for separating the different species present in the stock solution of BTXv, and we purified and characterized the collected species before use. We assessed the binding of these different species to FcRn in a cellular assay based on flow cytometry and surface plasmon resonance. HIC separated the different species of BTXv and allowed their collection at adequate levels of purity. Physicochemical characterization showed that species with higher levels of drug loading tended to form more aggregates. FcRn binding assays showed that the most conjugated species, particularly those with saturated loading, interacted more strongly than unconjugated BTXv with the FcRn.

  5. Targeting cancer cells with folic acid-iminoboronate fluorescent conjugates.

    Science.gov (United States)

    Cal, Pedro M S D; Frade, Raquel F M; Chudasama, Vijay; Cordeiro, Carlos; Caddick, Stephen; Gois, Pedro M P

    2014-05-25

    Herein we present the synthesis of fluorescent 2-acetylbenzeneboronic acids that undergo B-N promoted conjugation with lysozyme and N-(2-aminoethyl) folic acid (EDA-FA), generating conjugates that are selectively recognized and internalized by cancer cells that over-express folic acid receptors.

  6. Conjugated Bilirubin Differentially Regulates CD4+ T Effector Cells and T Regulatory Cell Function through Outside-In and Inside-Out Mechanisms: The Effects of HAV Cell Surface Receptor and Intracellular Signaling

    Science.gov (United States)

    Corral-Jara, Karla F.; Gómez-Leyva, Juan F.; Rosenstein, Yvonne; Jose-Abrego, Alexis; Roman, Sonia

    2016-01-01

    We recently reported an immune-modulatory role of conjugated bilirubin (CB) in hepatitis A virus (HAV) infection. During this infection the immune response relies on CD4+ T lymphocytes (TLs) and it may be affected by the interaction of HAV with its cellular receptor (HAVCR1/TIM-1) on T cell surface. How CB might affect T cell function during HAV infection remains to be elucidated. Herein, in vitro stimulation of CD4+ TLs from healthy donors with CB resulted in a decrease in the degree of intracellular tyrosine phosphorylation and an increase in the activity of T regulatory cells (Tregs) expressing HAVCR1/TIM-1. A comparison between CD4+ TLs from healthy donors and HAV-infected patients revealed changes in the TCR signaling pathway relative to changes in CB levels. The proportion of CD4+CD25+ TLs increased in patients with low CB serum levels and an increase in the percentage of Tregs expressing HAVCR1/TIM-1 was found in HAV-infected patients relative to controls. A low frequency of 157insMTTTVP insertion in the viral receptor gene HAVCR1/TIM-1 was found in patients and controls. Our data revealed that, during HAV infection, CB differentially regulates CD4+ TLs and Tregs functions by modulating intracellular pathways and by inducing changes in the proportion of Tregs expressing HAVCR1/TIM-1. PMID:27578921

  7. The collagen receptor uPARAP/Endo180 as a novel target for antibody-drug conjugate mediated treatment of mesenchymal and leukemic cancers

    DEFF Research Database (Denmark)

    Nielsen, Christoffer Fagernæs; van Putten, Sander Maarten; Lund, Ida Katrine

    2017-01-01

    A key task in developing the field of personalized cancer therapy is the identification of novel molecular targets that enable treatment of cancers not susceptible to other means of specific therapy. The collagen receptor uPARAP/Endo180 is overexpressed by malignant cells in several non-epithelia...

  8. A phospholipid-PEG2000 conjugate of a vascular endothelial growth factor receptor 2 (VEGFR2)-targeting heterodimer peptide for contrast-enhanced ultrasound imaging of angiogenesis.

    Science.gov (United States)

    Pillai, R; Marinelli, E R; Fan, H; Nanjappan, P; Song, B; von Wronski, M A; Cherkaoui, S; Tardy, I; Pochon, S; Schneider, M; Nunn, A D; Swenson, R E

    2010-03-17

    The transition of a targeted ultrasound contrast agent from animal imaging to testing in clinical studies requires considerable chemical development. The nature of the construct changes from an agent that is chemically attached to microbubbles to one where the targeting group is coupled to a phospholipid, for direct incorporation to the bubble surface. We provide an efficient method to attach a heterodimeric peptide to a pegylated phospholipid and show that the resulting construct retains nanomolar affinity for its target, vascular endothelial growth factor receptor 2 (VEGFR2), for both the human (kinase insert domain-containing receptor - KDR) and the mouse (fetal liver kinase 1 - Flk-1) receptors. The purified phospholipid-PEG-peptide isolated from TFA-based eluents is not stable with respect to hydrolysis of the fatty ester moieties. This leads to the time-dependent formation of the lysophospholipid and the phosphoglycerylamide derived from the degradation of the product. Purification of the product using neutral eluent systems provides a stable product. Methods to prepare the lysophospholipid (hydrolysis product) are also included. Biacore binding data demonstrated the retention of binding of the lipopeptide to the KDR receptor. The phospholipid-PEG2000-peptide is smoothly incorporated into gas-filled microbubbles and provides imaging of angiogenesis in a rat tumor model.

  9. Revisiting conjugate schedules.

    Science.gov (United States)

    MacAleese, Kenneth R; Ghezzi, Patrick M; Rapp, John T

    2015-07-01

    The effects of conjugate reinforcement on the responding of 13 college students were examined in three experiments. Conjugate reinforcement was provided via key presses that changed the clarity of pictures displayed on a computer monitor in a manner proportional to the rate of responding. Experiment 1, which included seven parameters of clarity change per response, revealed that responding decreased as the percentage clarity per response increased for all five participants. These results indicate that each participant's responding was sensitive to intensity change, which is a parameter of conjugate reinforcement schedules. Experiment 2 showed that responding increased during conjugate reinforcement phases and decreased during extinction phases for all four participants. Experiment 3 also showed that responding increased during conjugate reinforcement and further showed that responding decreased during a conjugate negative punishment condition for another four participants. Directions for future research with conjugate schedules are briefly discussed.

  10. Water-Soluble 8-Hydroxyquinoline Conjugate of Amino-Glucose As Receptor for La(3+) in HEPES Buffer, on Whatman Cellulose Paper and in Living Cells.

    Science.gov (United States)

    Areti, Sivaiah; Bandaru, Sateesh; Teotia, Rohit; Rao, Chebrolu P

    2015-12-15

    A water-soluble glucopyranosyl conjugate, L, has been synthesized and characterized by different analytical and spectral techniques. The L has been demonstrated to have switch-on fluorescence enhancement of ∼75 fold in the presence of La(3+) among the nine lanthanide ions studied in the HEPES buffer at pH 7.4. A minimum detection limit of 140 nM (16 ± 2 ppb) was shown by L for La(3+) in the buffer at physiological pH. The utility of L has been demonstrated by showing its sensitivity toward La(3+) on Whatman filter paper strips. The reversible and reusable action of L has been demonstrated by monitoring the fluorescence changes as a function of the addition of La(3+) followed by F(-) and HPO4(2-) ions. The complexation of L by La(3+) was shown by absorption spectra wherein isosbestic behavior was observed. The Job's plot suggests a 2:1 complex between L and La(3+), and the same was supported by ESI-MS. The control molecular study revealed the necessity of hydroxy quinoline and the amine group for La(3+) ion binding and the glyco-moiety to bring water solubility and biocompatibility. The structural features of the [2L+La(3+)] complex were established by DFT computational calculations. The chemo-ensemble, [2L+La(3+)], is shown responsible for providing intracellular fluorescence imaging in HepG2 cells.

  11. Part I. Naltrexone-derived conjugate addition ligands for opioid receptors. Part II. Chemical and enantioselective aspects of the metabolism of verapamil

    Energy Technology Data Exchange (ETDEWEB)

    Olsen, L.D.

    1987-01-01

    Selective chemoaffinity ligands to aid in identification and purification of opioid receptor subtypes were prepared from 6..cap alpha..- and 6..beta..-naltrexol, obtained stereoselectively from the ..mu..-receptor antagonist naltrexone. The targets were the 6..cap alpha..- and 6..beta..-methacrylate ethers and 6..cap alpha..- and 6..beta..-methacrylate esters prepared from reaction of 6..cap alpha..- and 6..beta..-naltrexol with methyl ..cap alpha..-(bromomethyl)acrylate or methacryloyl chloride. Of three methacrylate derivatives, the 6..cap alpha..-ether was the most potent in an opioid receptor binding assay with (/sup 3/H)-naltrexone. In the presence of sodium ion, preincubation of the 6..cap alpha..-ether resulted in recovery of about 60% of original (/sup 3/H)-naltrexone binding suggesting some irreversible effects. The methacrylate esters precipitated withdrawal in morphine dependent monkeys. The enantiomers of verapamil, a calcium channel antagonist, have different pharmacological and pharmacokinetic properties. The oxidative metabolism of verapamil was studied in rat and human liver microsomes and in man after a single oral dose.

  12. The Chemistry and Biology of Oligonucleotide Conjugates

    Science.gov (United States)

    Juliano, R.L.; Ming, Xin; Nakagawa, Osamu

    2012-01-01

    CONSPECTUS Short DNA or RNA oligonucleotides have tremendous potential as therapeutic agents. Because of their ability to engage in Watson-Crick base pairing they can interact with messenger mRNA or pre-mRNA targets with high selectivity and thus offer the possibility of precise manipulation of gene expression. This possibility has engendered extensive efforts to develop oligonucleotides as drugs, with many candidates already in clinical trials. However, a major impediment to the maturation of oligonucleotide-based therapeutics is the fact that these relatively large and usually highly charged molecules have great difficulty crossing cellular membranes and thus in penetrating to their sites of action in the cytosol or nucleus. In this Account we first summarize some basic aspects of the biology of antisense and siRNA oligonucleotides and then discuss chemical conjugation as an approach to improving the intracellular delivery and therapeutic potential of these agents. Our emphasis will be on the pharmacological ramifications of oligonucleotide conjugates rather than the details of conjugation chemistry. One important approach has been conjugation with ligands designed to bind to particular receptors and thus provide specificity to the interaction of cells with oligonucleotides. Another approach has been to couple antisense or siRNA with agents such as cell penetrating peptides that are designed to provoke escape of the conjugate from intracellular vesicular compartments. Both of these approaches have enjoyed some success. However, there remains much to be learned before oligonucleotide conjugates can find an important place in human therapeutics. PMID:22353142

  13. C3d-defined complement receptor-binding peptide p28 conjugated to circumsporozoite protein provides protection against Plasmodium berghei.

    Science.gov (United States)

    Bergmann-Leitner, Elke S; Duncan, Elizabeth H; Leitner, Wolfgang W; Neutzner, Albert; Savranskaya, Tatyana; Angov, Evelina; Tsokos, George C

    2007-11-01

    Immune response against circumsporozoite protein (CSP) of Plasmodium berghei, a major surface protein on the sporozoite, confers protection in various murine malaria models. Engineered DNA vaccine encoding CSP and 3 copies of C3d caused an unexpected loss in protection attributed to the binding of C3d to the C-terminal region of CSP. Because the C3d region known as p28 represents the complement receptor (CR) 2-binding motif, we developed a CSP-3 copies of p28 DNA construct (CSP-3p28). CSP-3p28-immunized mice were better protected against P. berghei sporozoites than CSP-immunized mice 6 weeks after the 2nd boost, produced sufficient IgG1 anti-CSP and CSP C-terminus antibody and failed to produce IgG2a. CSP-3C3d-immunized mice were not protected, failed to produce IgG1 and produced high amounts of IgG2a. We conclude that use of the CR2-binding motif of C3d as molecular adjuvant to CSP results in anti-malaria protective immune response probably by targeting the chimeric protein to CR2.

  14. Methotrexate and epirubicin conjugates as potential antitumor drugs

    Directory of Open Access Journals (Sweden)

    Szymon Wojciech Kmiecik

    2017-07-01

    Full Text Available Introduction: The use of hybrid molecules has become one of the most significant approaches in new cytotoxic drug design. This study describes synthesis and characterization of conjugates consisting of two well-known and characterized chemotherapeutic agents: methotrexate (MTX and epirubicin (EPR. The synthesized conjugates combine two significant anticancer strategies: combinatory therapy and targeted therapy. These two drugs were chosen because they have different mechanisms of action, which can increase the anticancer effect of the obtained conjugates. MTX, which is a folic acid analog, has high cytotoxic properties and can serve as a targeting moiety that can reach folate receptors (FRs overexpresing tumor cells. Combination of nonselective drugs such as EPR with MTX can increase the selectivity of the obtained conjugates, while maintaining the high cytotoxic properties.Materials and methods: Conjugates were purified by RP-HPLC and the structure was investigated by MS and MS/MS methods. The effect of the conjugates on proliferation of LoVo, LoVo/Dx, MCF-7 and MV-4-11 human cancer cell lines was determined by SRB or MTT assay.Results: The conjugation reaction results in the formation of monosubstituted (α, γ and disubstituted MTX derivatives. In vitro proliferation data demonstrate that the conjugates synthesized in our study show lower cytotoxic properties than both chemotherapeutics used alone.Discussion: Epirubicin cytotoxicity was not observed in obtained conjugates. Effective drugs release after internalization needs further investigation.

  15. Segmented conjugated polymers

    Indian Academy of Sciences (India)

    G Padmanaban; S Ramakrishnan

    2003-08-01

    Segmented conjugated polymers, wherein the conjugation is randomly truncated by varying lengths of non-conjugated segments, form an interesting class of polymers as they not only represent systems of varying stiffness, but also ones where the backbone can be construed as being made up of chromophores of varying excitation energies. The latter feature, especially when the chromophores are fluorescent, like in MEHPPV, makes these systems particularly interesting from the photophysics point of view. Segmented MEHPPV- samples, where x represents the mole fraction of conjugated segments, were prepared by a novel approach that utilizes a suitable precursor wherein selective elimination of one of the two eliminatable groups is affected; the uneliminated units serve as conjugation truncations. Control of the composition x of the precursor therefore permits one to prepare segmented MEHPPV- samples with varying levels of conjugation (elimination). Using fluorescence spectroscopy, we have seen that even in single isolated polymer chains, energy migration from the shorter (higher energy) chromophores to longer (lower energy) ones occurs – the extent of which depends on the level of conjugation. Further, by varying the solvent composition, it is seen that the extent of energy transfer and the formation of poorly emissive inter-chromophore excitons are greatly enhanced with increasing amounts of non-solvent. A typical S-shaped curve represents the variation of emission yields as a function of composition suggestive of a cooperative collapse of the polymer coil, reminiscent of conformational transitions seen in biological macromolecules.

  16. Qualidade conjugal: mapeando conceitos

    Directory of Open Access Journals (Sweden)

    Clarisse Mosmann

    2006-12-01

    Full Text Available Apesar da ampla utilização do conceito de qualidade conjugal, identifica-se falta de clareza conceitual acerca das variáveis que o compõem. Esse artigo apresenta revisão da literatura na área com o objetivo de mapear o conceito de qualidade conjugal. Foram analisadas sete principais teorias sobre o tema: Troca Social, Comportamental, Apego, Teoria da Crise, Interacionismo Simbólico. Pelos postulados propostos nas diferentes teorias, podem-se identificar três grupos de variáveis fundamentais na definição da qualidade conjugal: recursos pessoais dos cônjuges, contexto de inserção do casal e processos adaptativos. Neste sentido, a qualidade conjugal é resultado do processo dinâmico e interativo do casal, razão deste caráter multidimensional.

  17. Polymers for Protein Conjugation

    Directory of Open Access Journals (Sweden)

    Gianfranco Pasut

    2014-01-01

    Full Text Available Polyethylene glycol (PEG at the moment is considered the leading polymer for protein conjugation in view of its unique properties, as well as to its low toxicity in humans, qualities which have been confirmed by its extensive use in clinical practice. Other polymers that are safe, biodegradable and custom-designed have, nevertheless, also been investigated as potential candidates for protein conjugation. This review will focus on natural polymers and synthetic linear polymers that have been used for protein delivery and the results associated with their use. Genetic fusion approaches for the preparation of protein-polypeptide conjugates will be also reviewed and compared with the best known chemical conjugation ones.

  18. receptores

    Directory of Open Access Journals (Sweden)

    Salete Regina Daronco Benetti

    2006-01-01

    Full Text Available Se trata de un estudio etnográfico, que tuvo lo objetivo de interpretar el sistema de conocimiento y del significado atribuidos a la sangre referente a la transfusión sanguínea por los donadores y receptores de un banco de sangre. Para la colecta de las informaciones se observaron los participantes y la entrevista etnográfica se realizó el análisis de dominio, taxonómicos y temáticos. Los dominios culturales fueron: la sangre es vida: fuente de vida y alimento valioso; creencias religiosas: fuentes simbólicas de apoyos; donación sanguínea: un gesto colaborador que exige cuidarse, gratifica y trae felicidad; donación sanguínea: fuente simbólica de inseguridad; estar enfermo es una condición para realizar transfusión sanguínea; transfusión sanguínea: esperanza de vida; Creencias populares: transfusión sanguínea como riesgo para la salud; donadores de sangre: personas benditas; donar y recibir sangre: como significado de felicidad. Temática: “líquido precioso que origina, sostiene, modifica la vida, provoca miedo e inseguridad”.

  19. HER2 specific delivery of methotrexate by dendrimer conjugated anti-HER2 mAb

    Energy Technology Data Exchange (ETDEWEB)

    Shukla, Rameshwer; Thomas, Thommey P; Desai, Ankur M; Kotlyar, Alina; Park, Steve J; Baker, James R Jr [Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, 9220 MSRB III, Box 0648, Ann Arbor, MI 48109 (United States)], E-mail: rameshwe@umich.edu, E-mail: jbakerjr@med.umich.edu

    2008-07-23

    Herceptin, a humanized monoclonal antibody that binds to human growth factor receptor-2 (HER2), was covalently attached to a fifth-generation (G5) polyamidoamine dendrimer containing the cytotoxic drug methotrexate. The specific binding and internalization of this conjugate labeled with FITC was clearly demonstrated in cell lines overexpressing HER2 by flow cytometry as well as confocal microscopic analysis. In addition, binding and uptake of antibody conjugated dendrimers was completely blocked by excess non-conjugated herceptin. The dendrimer conjugate was also shown to inhibit the dihydrofolate reductase with similar activity to methotrexate. Co-localization experiments with lysotracker red indicate that antibody conjugate, although internalized efficiently into cells, has an unusually long residence time in the lysosome. Somewhat lower cytotoxicity of the conjugate in comparison to free methotrexate was attributed to the slow release of methotrexate from the conjugate and its long retention in the lysosomal pocket.

  20. Conjugation in "Escherichia coli"

    Science.gov (United States)

    Phornphisutthimas, Somkiat; Thamchaipenet, Arinthip; Panijpan, Bhinyo

    2007-01-01

    Bacterial conjugation is a genetic transfer that involves cell-to-cell between donor and recipient cells. With the current method used to teach students in genetic courses at the undergraduate level, the transconjugants are identified using bacterial physiology and/or antibiotic resistance. Using physiology, however, is difficult for both…

  1. DNA-cell conjugates

    Science.gov (United States)

    Hsiao, Shih-Chia; Francis, Matthew B.; Bertozzi, Carolyn; Mathies, Richard; Chandra, Ravi; Douglas, Erik; Twite, Amy; Toriello, Nicholas; Onoe, Hiroaki

    2016-05-03

    The present invention provides conjugates of DNA and cells by linking the DNA to a native functional group on the cell surface. The cells can be without cell walls or can have cell walls. The modified cells can be linked to a substrate surface and used in assay or bioreactors.

  2. Peptide-Carrier Conjugation

    DEFF Research Database (Denmark)

    Hansen, Paul Robert

    2015-01-01

    To produce antibodies against synthetic peptides it is necessary to couple them to a protein carrier. This chapter provides a nonspecialist overview of peptide-carrier conjugation. Furthermore, a protocol for coupling cysteine-containing peptides to bovine serum albumin is outlined....

  3. Theory of Digitized Conjugate Surface and Solution to Conjugate Surface

    Institute of Scientific and Technical Information of China (English)

    Xiao Lai-yuan; Liao Dao-xun; Yi Chuan-yun

    2004-01-01

    In order to meet the needs of designing and processing digitized surfaces, the method to spreading digitized surface has been proposed. The key technique is to solve the problem of digitized conjugate surface. In the paper, the digitized conjugate surface was theoretically investigated, and the solution of conjugate surface based on digitized surface was also studied. The digitized conjugate surface theory was then proposed, and applied to build the model of solving conjugate surface based on digitized surface. A corresponding algorithm was developed. This paper applies the software Conjugater-1.0 that is developed by ourselves to compute the digitized conjugate surfaces of the drum-tooth surface. This study provides theoretical and technical bases for analyzing engagement of digitized surface, simulation and numerical processing technique.

  4. Peptide conjugation: before or after nanoparticle formation?

    Science.gov (United States)

    Valetti, Sabrina; Mura, Simona; Noiray, Magali; Arpicco, Silvia; Dosio, Franco; Vergnaud, Juliette; Desmaële, Didier; Stella, Barbara; Couvreur, Patrick

    2014-11-19

    We report herein a detailed study concerning the impact of different bioconjugation and nanoformulation strategies on the in vitro targeting ability of peptide-decorated squalenoyl gemcitabine (SQdFdC) nanoparticles (NPs). NPs have been functionalized with the CKAAKN peptide, previously identified as an efficient homing device within the pancreatic pathological microenvironment. Two approaches have been followed: (i) either the CKAAKN peptide was directly conjugated at the surface of preformed SQdFdC nanoparticles (conjugation after NP formation) or (ii) it was first reacted with a maleimide squalenoyl derivative before the resulting bioconjugate was co-nanoprecipitated with SQdFdC to form the peptide-decorated NPs (conjugation before NP formation). NPs were characterized with respect to mean diameter, zeta potential, and stability over time. Then, their specific interaction with the sFRP-4 protein was evaluated by surface plasmon resonance. Although both synthetic strategies allowed us to formulate NPs able to interact with the corresponding receptor, enhanced target binding and better specific avidity were observed with CKAAKN-NPs functionalized before NP formation. These NPs displayed the highest cell uptake and cytotoxicity in an in vitro model of human MIA Paca-2 pancreatic cancer cells.

  5. Cancer Chemopreventive Ability of Conjugated Linolenic Acids

    Directory of Open Access Journals (Sweden)

    Kazuo Miyashita

    2011-11-01

    Full Text Available Conjugated fatty acids (CFA have received increased interest because of their beneficial effects on human health, including preventing cancer development. Conjugated linoleic acids (CLA are such CFA, and have been reviewed extensively for their multiple biological activities. In contrast to other types of CFAs including CLA that are found at low concentrations (less than 1% in natural products, conjugated linolenic acids (CLN are the only CFAs that occur in higher quantities in natural products. Some plant seeds contain a considerably high concentration of CLN (30 to 70 wt% lipid. Our research group has screened CLN from different plant seed oils to determine their cancer chemopreventive ability. This review describes the physiological functions of CLN isomers that occur in certain plant seeds. CLN are able to induce apoptosis through decrease of Bcl-2 protein in certain human cancer cell lines, increase expression of peroxisome proliferator-activated receptor (PPAR-γ, and up-regulate gene expression of p53. Findings in our preclinical animal studies have indicated that feeding with CLN resulted in inhibition of colorectal tumorigenesis through modulation of apoptosis and expression of PPARγ and p53. In this review, we summarize chemopreventive efficacy of CLN against cancer development, especially colorectal cancer.

  6. Role of outer-membrane proteins and lipopolysaccharide in conjugation between Neisseria gonorrhoeae and Neisseria cinerea.

    Science.gov (United States)

    Genco, C A; Clark, V L

    1988-12-01

    Little is known concerning the mechanism involved in cell contact between the donor and recipient during conjugation in Neisseria gonorrhoeae. The formation of stable mating pairs during conjugation in Escherichia coli appears to require a specific protein as well as LPS in the outer membrane of the recipient cell. To attempt to identify the cell surface components necessary for conjugation in the neisseriae, we began a comparison of the outer membrane of Neisseria cinerea strains that can (Con+) and cannot (Con-) serve as recipients in conjugation with N. gonorrhoeae. There were no differences in outer-membrane protein profiles on SDS-polyacrylamide gel electrophoresis between Con+ and Con- strains that could be correlated with the ability to conjugate. However, whole outer membrane isolated from Con+ strains specifically inhibited conjugation while those from Con- strains did not. Proteolytic cleavage of outer-membrane proteins by trypsin, pronase or alpha-chymotrypsin abolished the inhibitory effect of Con+ outer membranes, suggesting that these outer membranes contained a protease-sensitive protein(s) involved in conjugation. Although periodate oxidation of Con+ outer-membrane carbohydrates did not abolish the inhibitory action of these membranes, purified LPS from both Con+ and Con- strains inhibited conjugation when added at low concentrations. These results suggest that conjugation requires the presence of a specific conjugal receptor that consists of both LPS and one or more outer-membrane proteins. Both Con+ and Con- strains contain the necessary LPS, but only Con+ strains contain the required protein(s).

  7. A water soluble vitamin B12-ReI fluorescent conjugate for cell uptake screens: use in the confirmation of cubilin in the lung cancer line A549.

    Science.gov (United States)

    Vortherms, Anthony R; Kahkoska, Anna R; Rabideau, Amy E; Zubieta, Jon; Andersen, Louise Lund; Madsen, Mette; Doyle, Robert P

    2011-09-21

    A water soluble vitamin B(12)-rhenium conjugate was synthesized and used in concert with intrinsic factor to screen for cubilin receptor-mediated uptake in lung cancer cells. Internalization of the conjugate demonstrated that it could be used to rapidly screen for the cubilin receptor in living cells, subsequently confirmed with Western blotting and RT-PCR.

  8. Organometallic B12-DNA conjugate

    DEFF Research Database (Denmark)

    Hunger, Miriam; Mutti, Elena; Rieder, Alexander

    2014-01-01

    Design, synthesis, and structural characterization of a B12-octadecanucleotide are presented herein, a new organometallic B12-DNA conjugate. In such covalent conjugates, the natural B12 moiety may be a versatile vector for controlled in vivo delivery of oligonucleotides to cellular targets in hum...

  9. Conjugate-SELEX: A High-throughput Screening of Thioaptamer-liposomal Nanoparticle Conjugates for Targeted Intracellular Delivery of Anticancer Drugs.

    Science.gov (United States)

    Mu, Qingshan; Annapragada, Akshaya; Srivastava, Mayank; Li, Xin; Wu, Jean; Thiviyanathan, Varatharasa; Wang, Hongyu; Williams, Alexander; Gorenstein, David; Annapragada, Ananth; Vigneswaran, Nadarajah

    2016-11-01

    Patients with advanced head and neck squamous cell carcinoma receiving chemotherapy have a poor prognosis partly due to normal tissue toxicity; therefore, development of a tumor-targeted drug delivery platform to minimize collateral toxicity is a goal of cancer nanomedicine. Aptamers can achieve this purpose. While conventional Systematic Evolution of Ligands by Exponential Enrichment (SELEX) screens aptamer-only libraries and conjugates them to delivery vehicles after selection, we hypothesized that specific delivery requires screening libraries with aptamer-nanoparticle conjugates. We designed a procedure called, "Conjugate-SELEX", where liposomal nanoparticles (LNP) conjugated with aptamers is screened to identify aptamers that carried attached LNPs to the human head and neck squamous cell carcinoma cell cytosol. Aptamer-LNPs were simultaneously selected for a low affinity to human hepatocytes, minimizing hepatoxicity and LNP clearance. Post-SELEX Next Generation sequencing demonstrated convergence to a family of sequences with one base difference. Affinity pulldown and proteomics analysis identified the uptake-mediating surface receptor as the neuroblast differentiation-associated protein AHNAK (Desmoyokin), a ubiquitous intracellular protein expressed in certain epithelial cell types. Uptake studies with the lead aptamer-conjugates showed enhanced uptake and increased cytotoxicity induced by doxorubicin in cells treated with aptamer-conjugated LNPs over LNP controls. Conjugate-SELEX identifies aptamers capable of targeted cytosolic delivery of attached LNPs payload, while minimizing off-target delivery. The technique lends itself to identification of uptake-mediating surface receptors.

  10. Hierarchically deflated conjugate residual

    CERN Document Server

    Yamaguchi, Azusa

    2016-01-01

    We present a progress report on a new class of multigrid solver algorithm suitable for the solution of 5d chiral fermions such as Domain Wall fermions and the Continued Fraction overlap. Unlike HDCG \\cite{Boyle:2014rwa}, the algorithm works directly on a nearest neighbour fine operator. The fine operator used is Hermitian indefinite, for example $\\Gamma_5 D_{dwf}$, and convergence is achieved with an indefinite matrix solver such as outer iteration based on conjugate residual. As a result coarse space representations of the operator remain nearest neighbour, giving an 8 point stencil rather than the 81 point stencil used in HDCG. It is hoped this may make it viable to recalculate the matrix elements of the little Dirac operator in an HMC evolution.

  11. Dihydroazulene-buckminsterfullerene conjugates

    DEFF Research Database (Denmark)

    Santella, Marco; Mazzanti, Virginia; Jevric, Martyn;

    2012-01-01

    The dihydroazulene (DHA)/vinylheptafulvene (VHF) photo/thermoswitch has recently attracted interest as a molecular switch for molecular electronics. In this field, Buckminsterfullerene, C(60), has been shown to be a useful anchoring group for adhering a molecular wire to an electrode. Here we have...... combined the two units with the overall aim to elucidate how C(60) influences the DHA-VHF switching events. Efficient synthetic protocols for making covalently linked DHA-C(60) conjugates were developed, using Prato, Sonogashira, Hay, and Cadiot-Chodkiewicz reactions. These syntheses provide as well...... of DHA to its corresponding VHF. Thus, C(60) was found to significantly quench this conversion when situated closely to the DHA unit....

  12. Generalized conjugate gradient squared

    Energy Technology Data Exchange (ETDEWEB)

    Fokkema, D.R.; Sleijpen, G.L.G. [Utrecht Univ. (Netherlands)

    1994-12-31

    In order to solve non-symmetric linear systems of equations, the Conjugate Gradient Squared (CGS) is a well-known and widely used iterative method. In practice the method converges fast, often twice as fast as the Bi-Conjugate Gradient method. This is what you may expect, since CGS uses the square of the BiCG polynomial. However, CGS may suffer from its erratic convergence behavior. The method may diverge or the approximate solution may be inaccurate. BiCGSTAB uses the BiCG polynomial and a product of linear factors in an attempt to smoothen the convergence. In many cases, this has proven to be very effective. Unfortunately, the convergence of BiCGSTAB may stall when a linear factor (nearly) degenerates. BiCGstab({ell}) is designed to overcome this degeneration of linear factors. It generalizes BiCGSTAB and uses both the BiCG polynomial and a product of higher order factors. Still, CGS may converge faster than BiCGSTAB or BiCGstab({ell}). So instead of using a product of linear or higher order factors, it may be worthwhile to look for other polynomials. Since the BiCG polynomial is based on a three term recursion, a natural choice would be a polynomial based on another three term recursion. Possibly, a suitable choice of recursion coefficients would result in method that converges faster or as fast as CGS, but less erratic. It turns out that an algorithm for such a method can easily be formulated. One particular choice for the recursion coefficients leads to CGS. Therefore one could call this algorithm generalized CGS. Another choice for the recursion coefficients leads to BiCGSTAB. It is therefore possible to mix linear factors and some polynomial based on a three term recursion. This way one may get the best of both worlds. The authors will report on their findings.

  13. GPCR ligand-dendrimer (GLiDe) conjugates: future smart drugs?

    Science.gov (United States)

    Jacobson, Kenneth A

    2010-12-01

    Unlike nanocarriers that are intended to release their drug cargo at the site of action, biocompatibile polyamidoamine (PAMAM) conjugates are designed to act at cell surface G protein-coupled receptors (GPCRs) without drug release. These multivalent GPCR ligand-dendrimer (GLiDe) conjugates display qualitatively different pharmacological properties in comparison with monomeric drugs. They might be useful as novel tools to study GPCR homodimers and heterodimers as well as higher aggregates. The structure of the conjugate determines the profile of biological activity, receptor selectivity, and physical properties such as water solubility. Prosthetic groups for characterization and imaging of receptors can be introduced without loss of affinity. The feasibility of targeting multiple adenosine and P2Y receptors for synergistic effects has been shown. Testing in vivo will be needed to explore the effects on pharmacokinetics and tissue targeting.

  14. Tocilizumab - Alendronate Conjugate for Treatment of Rheumatoid Arthritis.

    Science.gov (United States)

    Lee, Hwiwon; Bhang, Suk Ho; Lee, Jeong Ho; Kim, Hyemin; Hahn, Sei Kwang

    2017-01-20

    An autoimmune disease of rheumatoid arthritis (RA) causes severe inflammation on the synovial membrane, which results in the destruction of articular cartilage and bone. Here, Tocilizumab (TCZ) - Alendronate (ALD) conjugate is synthesized for the early intervention of RA. A humanized monoclonal antibody of TCZ shows an immunosuppressive effect, targeting interleukin-6 (IL-6) receptor in the RA pathogenesis. ALD is an anti-inflammatory bisphosphonate drug which can bind to the exposed bone surface. ALD is conjugated selectively to N-glycan on Fc region of TCZ using a chemical linker of 3-(2-pyridyldithio) propionyl hydrazide (PDPH) - poly(ethylene glycol) - N-hydroxysuccinimide (PDPH-PEG-NHS). The successful synthesis of TCZ-ALD conjugate is corroborated by 1H NMR, the purpald assay, mass spectrometry (MS), and high performance liquid chromatography (HPLC). In vitro binding affinity and cell viability tests confirmed the biological activity of TCZ-ALD conjugate. Furthermore, in vivo efficacy of TCZ-ALD conjugate is confirmed by micro computed tomography (CT), histological, and western blot analyses for the treatment of RA.

  15. Adenosine conjugated lipidic nanoparticles for enhanced tumor targeting.

    Science.gov (United States)

    Swami, Rajan; Singh, Indu; Jeengar, Manish Kumar; Naidu, V G M; Khan, Wahid; Sistla, Ramakrishna

    2015-01-01

    Delivering chemotherapeutics by nanoparticles into tumor is impeded majorly by two factors: nonspecific targeting and inefficient penetration. Targeted delivery of anti-cancer agents solely to tumor cells introduces a smart strategy because it enhances the therapeutic index compared with untargeted drugs. The present study was performed to investigate the efficiency of adenosine (ADN) to target solid lipid nanoparticles (SLN) to over expressing adenosine receptor cell lines such as human breast cancer and prostate cancer (MCF-7 and DU-145 cells), respectively. SLN were prepared by emulsification and solvent evaporation process using docetaxel (DTX) as drug and were characterized by various techniques like dynamic light scattering, differential scanning calorimeter and transmission electron microscopy. DTX loaded SLNs were surface modified with ADN, an adenosine receptors ligand using carbodiimide coupling. Conjugation was confirmed using infrared spectroscopy and quantified using phenol-sulfuric acid method. Conjugated SLN were shown to have sustained drug release as compared to unconjugated nanoparticles and drug suspension. Compared with free DTX and unconjugated SLN, ADN conjugated SLN showed significantly higher cytotoxicity of loaded DTX, as evidenced by in vitro cell experiments. The IC50 was 0.41 μg/ml for native DTX, 0.30 μg/ml for unconjugated SLN formulation, and 0.09 μg/ml for ADN conjugated SLN formulation in MCF-7 cell lines. Whereas, in DU-145, there was 2 fold change in IC50 of ADN-SLN as compared to DTX. IC50 was found to be 0.44 μg/ml for free DTX, 0.39 μg/ml for unconjugated SLN and 0.22 μg/ml for ADN-SLN. Annexin assay and cell cycle analysis assay further substantiated the cell cytotoxicity. Fluorescent cell uptake and competitive ligand-receptor binding assay corroborated the receptor mediated endocytosis pathway indicated role of adenosine receptors in internalization of conjugated particles. Pharmacokinetic studies of lipidic

  16. Solution Structure and Constrained Molecular Dynamics Study of Vitamin B12 Conjugates of the Anorectic Peptide PYY(3-36).

    Science.gov (United States)

    Henry, Kelly E; Kerwood, Deborah J; Allis, Damian G; Workinger, Jayme L; Bonaccorso, Ron L; Holz, George G; Roth, Christian L; Zubieta, Jon; Doyle, Robert P

    2016-05-06

    Vitamin B12 -peptide conjugates have considerable therapeutic potential through improved pharmacokinetic and/or pharmacodynamic properties imparted on the peptide upon covalent attachment to vitamin B12 (B12 ). There remains a lack of structural studies investigating the effects of B12 conjugation on peptide secondary structure. Determining the solution structure of a B12 -peptide conjugate or conjugates and measuring functions of the conjugate(s) at the target peptide receptor may offer considerable insight concerning the future design of fully optimized conjugates. This methodology is especially useful in tandem with constrained molecular dynamics (MD) studies, such that predictions may be made about conjugates not yet synthesized. Focusing on two B12 conjugates of the anorectic peptide PYY(3-36), one of which was previously demonstrated to have improved food intake reduction compared with PYY(3-36), we performed NMR structural analyses and used the information to conduct MD simulations. The study provides rare structural insight into vitamin B12 conjugates and validates the fact that B12 can be conjugated to a peptide without markedly affecting peptide secondary structure.

  17. Polymer decorated gold nanoparticles in nanomedicine conjugates.

    Science.gov (United States)

    Capek, Ignác

    2017-02-15

    Noble metal, especially gold nanoparticles and their conjugates with biopolymers have immense potential for disease diagnosis and therapy on account of their surface plasmon resonance (SPR) enhanced light scattering and absorption. Conjugation of noble metal nanoparticles to ligands specifically targeted to biomarkers on diseased cells allows molecular-specific imaging and detection of disease. The development of smart gold nanoparticles (AuNPs) that can deliver therapeutics at a sustained rate directly to cancer cells may provide better efficacy and lower toxicity for treating cancer tumors. We highlight some of the promising classes of targeting systems that are under development for the delivery of gold nanoparticles. Nanoparticles designed for biomedical applications are often coated with polymers containing reactive functional groups to conjugate targeting ligands, cell receptors or drugs. Using targeted nanoparticles to deliver chemotherapeutic agents in cancer therapy offers many advantages to improve drug/gene delivery and to overcome many problems associated with conventional radiotherapy and chemotherapy. The targeted nanoparticles were found to be effective in killing cancer cells which were studied using various anticancer assays. Cell morphological analysis shows the changes occurred in cancer cells during the treatment with AuNPs. The results determine the influence of particle size and concentration of AuNPs on their absorption, accumulation, and cytotoxicity in model normal and cancer cells. As the mean particle diameter of the AuNPs decreased, their rate of absorption by the intestinal epithelium cells increased. These results provide important insights into the relationship between the dimensions of AuNPs and their gastrointestinal uptake and potential cytotoxicity. Furthermore gold nanoparticles efficiently convert the absorbed light into localized heat, which can be exploited for the selective laser photothermal therapy of cancer. We also review

  18. Aptamer-Drug Conjugates.

    Science.gov (United States)

    Zhu, Guizhi; Niu, Gang; Chen, Xiaoyuan

    2015-11-18

    Western medicine often aims to specifically treat diseased tissues or organs. However, the majority of current therapeutics failed to do so owing to their limited selectivity and the consequent "off-target" side effects. Targeted therapy aims to enhance the selectivity of therapeutic effects and reduce adverse side effects. One approach toward this goal is to utilize disease-specific ligands to guide the delivery of less-specific therapeutics, such that the therapeutic effects can be guided specifically to diseased tissues or organs. Among these ligands, aptamers, also known as chemical antibodies, have emerged over the past decades as a novel class of targeting ligands that are capable of specific binding to disease biomarkers. Compared with other types of targeting ligands, aptamers have an array of unique advantageous features, which make them promising for developing aptamer-drug conjugates (ApDCs) for targeted therapy. In this Review, we will discuss ApDCs for targeted drug delivery in chemotherapy, gene therapy, immunotherapy, photodynamic therapy, and photothermal therapy, primarily of cancer.

  19. Sequential measurements of conjugate observables

    Energy Technology Data Exchange (ETDEWEB)

    Carmeli, Claudio [Dipartimento di Fisica, Universita di Genova, Via Dodecaneso 33, 16146 Genova (Italy); Heinosaari, Teiko [Department of Physics and Astronomy, Turku Centre for Quantum Physics, University of Turku, 20014 Turku (Finland); Toigo, Alessandro, E-mail: claudio.carmeli@gmail.com, E-mail: teiko.heinosaari@utu.fi, E-mail: alessandro.toigo@polimi.it [Dipartimento di Matematica ' Francesco Brioschi' , Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano (Italy)

    2011-07-15

    We present a unified treatment of sequential measurements of two conjugate observables. Our approach is to derive a mathematical structure theorem for all the relevant covariant instruments. As a consequence of this result, we show that every Weyl-Heisenberg covariant observable can be implemented as a sequential measurement of two conjugate observables. This method is applicable both in finite- and infinite-dimensional Hilbert spaces, therefore covering sequential spin component measurements as well as position-momentum sequential measurements.

  20. A comparison of three (67/68)Ga-labelled exendin-4 derivatives for β-cell imaging on the GLP-1 receptor: the influence of the conjugation site of NODAGA as chelator.

    NARCIS (Netherlands)

    Jodal, A.; Lankat-Buttgereit, B.; Brom, M.; Schibli, R.; Behe, M.

    2014-01-01

    Various diseases derive from pathologically altered β-cells. Their function can be increased, leading to hyperinsulinism, or decreased, resulting in diabetes. Non-invasive imaging of the β-cell-specific glucagon-like peptide receptor-1 (GLP-1R) would allow the assessment of both β-cell mass and deri

  1. Hacking into the granuloma: could antibody antibiotic conjugates be developed for TB?

    Science.gov (United States)

    Ekins, Sean

    2014-12-01

    Alternatives to small molecule or vaccine approaches to treating tuberculosis are rarely discussed. Attacking Mycobacterium tuberculosis in the granuloma represents a challenge. It is proposed that the conjugation of small molecules onto a monoclonal antibody that recognizes macrophage or lymphocytes cell surface receptors, might be a way to target the bacteria in the granuloma. This antibody drug conjugate approach is currently being used in 2 FDA approved targeted cancer therapies. The pros and cons of this proposal for further research are discussed.

  2. Targeted images of KB cells using folate-conjugated gold nanoparticles

    Science.gov (United States)

    Rathinaraj, Pierson; Lee, Kyubae; Park, Soo-Young; Kang, Inn-Kyu

    2015-01-01

    Mercaptosuccinic acid-coated gold (GM) nanoparticles were prepared and characterized by transmission electron microscopy and dynamic light scattering. Folic acid (F) was then conjugated to the GM to preferentially target oral squamous cancer (KB) cells with folate receptors expressed on their membranes and facilitate the transit of the nanoparticles across the cell membrane. Finally, a fluorescence dye (Atto) was conjugated to the nanoparticles to visualize their internalization into KB cells. After culture of the cells in a medium containing GM and folate-conjugated GM (GF), the interaction of surface-modified gold nanoparticles with KB cells was studied.

  3. High-conjugation-efficiency aqueous CdSe quantum dots.

    Science.gov (United States)

    Au, Giang H T; Shih, Wan Y; Shih, Wei-Heng

    2013-11-12

    Quantum dots (QDs) are photoluminescent nanoparticles that can be directly or indirectly coupled with a receptor such as an antibody to specifically image a target biomolecule such as an antigen. Recent studies have shown that QDs can be directly made at room temperature and in an aqueous environment (AQDs) with 3-mercaptopropionic acid (MPA) as the capping ligand without solvent and ligand exchange typically required by QDs made by the organic solvent routes (OQDs). In this study, we have synthesized CdSe AQDs and compared their conjugation efficiency and imaging efficacy with commercial carboxylated OQDs in HT29 colon cancer cells using a primary antibody-biotinylated secondary antibody-streptavidin (SA) sandwich. We showed that the best imaging condition for AQDs occurred when one AQD was bound with 3 ± 0.3 SA with a nominal SA/AQD ratio of 4 corresponding to an SA conjugation efficiency of 75 ± 7.5%. In comparison, for commercial CdSe-ZnS OQDs to achieve 2.7 ± 0.4 bound SAs per OQD for comparable imaging efficacy a nominal SA/OQD ratio of 80 was needed corresponding to an SA conjugation efficiency of 3.4 ± 0.5% for CdSe-ZnS OQDs. The more than 10 times better SA conjugation efficiency of the CdSe AQDs as compared to that of the CdSe-ZnS OQDs was attributed to more capping molecules on the AQD surface as a result of the direct aqueous synthesis. More capping molecules on the AQD surface also allowed the SA-AQD conjugate to be stable in cell culture medium for more than three days without losing their staining capability in a flowing cell culture medium. In contrast, SA-OQD conjugates aggregated in cell culture medium and in phosphate buffer saline solution over time.

  4. Research study of conjugate materials; Conjugate material no chosa kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-03-01

    The paper reported an introductory research on possibilities of new glass `conjugate materials.` The report took up the structure and synthetic process of conjugate materials to be researched/developed, classified them according to structural elements on molecular, nanometer and cluster levels, and introduced the structures and functions. Further, as glasses with new functions to be proposed, the paper introduced transparent and high-strength glass used for houses and vehicles, light modulation glass which realizes energy saving and optical data processing, and environmentally functional glass which realizes environmental cleaning or high performance biosensor. An initial survey was also conducted on rights of intellectual property to be taken notice of in Japan and abroad in the present situation. Reports were summed up and introduced of Osaka National Research Institute, Electrotechnical Laboratory, and National Industrial Research Institute of Nagoya which are all carrying out leading studies of conjugate materials. 235 refs., 135 figs., 6 tabs.

  5. Conjugated polymer nanoparticles, methods of using, and methods of making

    KAUST Repository

    Habuchi, Satoshi

    2017-03-16

    Embodiments of the present disclosure provide for conjugated polymer nanoparticle, method of making conjugated polymer nanoparticles, method of using conjugated polymer nanoparticle, polymers, and the like.

  6. Targeting the Eph System with Peptides and Peptide Conjugates.

    Science.gov (United States)

    Riedl, Stefan J; Pasquale, Elena B

    2015-01-01

    Eph receptor tyrosine kinases and ephrin ligands constitute an important cell communication system that controls development, tissue homeostasis and many pathological processes. Various Eph receptors/ephrins are present in essentially all cell types and their expression is often dysregulated by injury and disease. Thus, the 14 Eph receptors are attracting increasing attention as a major class of potential drug targets. In particular, agents that bind to the extracellular ephrin-binding pocket of these receptors show promise for medical applications. This pocket comprises a broad and shallow groove surrounded by several flexible loops, which makes peptides particularly suitable to target it with high affinity and selectivity. Accordingly, a number of peptides that bind to Eph receptors with micromolar affinity have been identified using phage display and other approaches. These peptides are generally antagonists that inhibit ephrin binding and Eph receptor/ ephrin signaling, but some are agonists mimicking ephrin-induced Eph receptor activation. Importantly, some of the peptides are exquisitely selective for single Eph receptors. Most identified peptides are linear, but recently the considerable advantages of cyclic scaffolds have been recognized, particularly in light of potential optimization towards drug leads. To date, peptide improvements have yielded derivatives with low nanomolar Eph receptor binding affinity, high resistance to plasma proteases and/or long in vivo half-life, exemplifying the merits of peptides for Eph receptor targeting. Besides their modulation of Eph receptor/ephrin function, peptides can also serve to deliver conjugated imaging and therapeutic agents or various types of nanoparticles to tumors and other diseased tissues presenting target Eph receptors.

  7. Conjugate Gradient with Subspace Optimization

    CERN Document Server

    Karimi, Sahar

    2012-01-01

    In this paper we present a variant of the conjugate gradient (CG) algorithm in which we invoke a subspace minimization subproblem on each iteration. We call this algorithm CGSO for "conjugate gradient with subspace optimization". It is related to earlier work by Nemirovsky and Yudin. We apply the algorithm to solve unconstrained strictly convex problems. As with other CG algorithms, the update step on each iteration is a linear combination of the last gradient and last update. Unlike some other conjugate gradient methods, our algorithm attains a theoretical complexity bound of $O(\\sqrt{L/l} \\log(1/\\epsilon))$, where the ratio $L/l$ characterizes the strong convexity of the objective function. In practice, CGSO competes with other CG-type algorithms by incorporating some second order information in each iteration.

  8. Persistence Mechanisms of Conjugative Plasmids

    DEFF Research Database (Denmark)

    Bahl, Martin Iain; Hansen, Lars H.; Sørensen, Søren Johannes

    2009-01-01

    Are plasmids selfish parasitic DNA molecules or an integrated part of the bacterial genome? This chapter reviews the current understanding of the persistence mechanisms of conjugative plasmids harbored by bacterial cells and populations. The diversity and intricacy of mechanisms affecting...... the successful propagation and long-term continued existence of these extra-chromosomal elements is extensive. Apart from the accessory genetic elements that may provide plasmid-harboring cells a selective advantage, special focus is placed on the mechanisms conjugative plasmids employ to ensure their stable...... maintenance in the host cell. These importantly include the ability to self-mobilize in a process termed conjugative transfer, which may occur across species barriers. Other plasmid stabilizing mechanisms include the multimer resolution system, active partitioning, and post-segregational-killing of plasmid...

  9. Hypercube Solutions for Conjugate Directions

    Science.gov (United States)

    1991-12-01

    alternative term that emphasizes the role of A in this definition. We also say that x and y are A-orthogonal. [Ref. 18: p. 410] The method of conjugate...conjugate (A-orthogonal). begin CG u0 =zeros(n) (arbitrary initial guess) Po = r0 = b- Auo for i = 0 : n = pTAp , (denominator used below) ai = (pTri...application, it could characterize water or chemical penetration in soil. We shall continue to use the term "heat equation", though, for the sake of

  10. On contravariant product conjugate connections

    Directory of Open Access Journals (Sweden)

    A. M. Blaga

    2012-02-01

    Full Text Available Invariance properties for the covariant and contravariant connections on a Riemannian manifold with respect to an almost product structure are stated. Restricting to a distribution of the contravariant connections is also discussed. The particular case of the conjugate connection is investigated and properties of the extended structural and virtual tensors for the contravariant connections are given.

  11. Actinomycete integrative and conjugative elements

    NARCIS (Netherlands)

    Poele, Evelien M. te; Bolhuis, Henk; Dijkhuizen, Lubbert

    2008-01-01

    This paper reviews current knowledge on actinomycete integrative and conjugative elements (AICEs). The best characterised AICEs, pSAM2 of Streptomyces ambofaciens (10.9 kb), SLP1 (17.3 kb) of Streptomyces coelicolor and pMEA300 of Amycolatopsis methanolica (13.3 kb), are present as integrative eleme

  12. Glutathione conjugation as a bioactivation reaction

    NARCIS (Netherlands)

    Bladeren, P.J. van

    2000-01-01

    In general, glutathione conjugation is regarded as a detoxication reaction. However, depending on the properties of the substrate, bioactivation is also possible. Four types of activation reaction have been recognized: direct-acting compounds, conjugates that are activated through cysteine conjugate

  13. Glutathione conjugation as a bioactivation reaction

    NARCIS (Netherlands)

    Bladeren, P.J. van

    2000-01-01

    In general, glutathione conjugation is regarded as a detoxication reaction. However, depending on the properties of the substrate, bioactivation is also possible. Four types of activation reaction have been recognized: direct-acting compounds, conjugates that are activated through cysteine conjugate

  14. Bacteriophytochromes control conjugation in Agrobacterium fabrum.

    Science.gov (United States)

    Bai, Yingnan; Rottwinkel, Gregor; Feng, Juan; Liu, Yiyao; Lamparter, Tilman

    2016-08-01

    Bacterial conjugation, the transfer of single stranded plasmid DNA from donor to recipient cell, is mediated through the type IV secretion system. We performed conjugation assays using a transmissible artificial plasmid as reporter. With this assay, conjugation in Agrobacterium fabrum was modulated by the phytochromes Agp1 and Agp2, photoreceptors that are most sensitive in the red region of visible light. In conjugation studies with wild-type donor cells carrying a pBIN-GUSINT plasmid as reporter that lacked the Ti (tumor inducing) plasmid, no conjugation was observed. When either agp1(-) or agp2(-) knockout donor strains were used, plasmid DNA was delivered to the recipient, indicating that both phytochromes suppress conjugation in the wild type donor. In the recipient strains, the loss of Agp1 or Agp2 led to diminished conjugation. When wild type cells with Ti plasmid and pBIN-GUS reporter plasmid were used as donor, a high rate of conjugation was observed. The DNA transfer was down regulated by red or far-red light by a factor of 3.5. With agp1(-) or agp2(-) knockout donor cells, conjugation in the dark was about 10 times lower than with the wild type donor, and with the double knockout donor no conjugation was observed. These results imply that the phytochrome system has evolved to inhibit conjugation in the light. The decrease of conjugation under different temperature correlated with the decrease of phytochrome autophosphorylation.

  15. Biotin/Folate-decorated Human Serum Albumin Nanoparticles of Docetaxel: Comparison of Chemically Conjugated Nanostructures and Physically Loaded Nanoparticles for Targeting of Breast Cancer.

    Science.gov (United States)

    Nateghian, Navid; Goodarzi, Navid; Amini, Mohsen; Atyabi, Fatemeh; Khorramizadeh, Mohammad Reza; Dinarvand, Rassoul

    2016-01-01

    Docetaxel (DTX) is a widely used chemotherapeutic agent with very low water solubility. Conjugation of DTX to human serum albumin (HSA) is an effective way to increase its water solubility. Attachment of folic acid (FA) or biotin as targeting moieties to DTX-HSA conjugates may lead to active targeting and specific uptake by cancer cells with overexpressed FA or biotin receptors. In this study, FA or biotin molecules were attached to DTX-HSA conjugates by two different methods. In one method, FA or biotin molecules were attached to remaining NH2 residues of HSA in DTX-HSA conjugate by covalent bonds. In the second method, HSA-FA or HSA-biotin conjugates were synthesized separately and then combined by DTX-HSA conjugate in proper ratio to prepare nanoparticles containing DTX-HSA plus HSA-FA or HSA-biotin. Cell viability of different nanoparticle was evaluated on MDA-MB-231 (folate receptor positive), A549 (folate receptor negative), and 4T1 (biotin receptor positive) and showed superior cytotoxicity compared with free docetaxel (Taxotere). In vivo studies of DTX-HSA-FA and DTX-HSA-biotin conjugates in BULB/c mice, tumorized by 4T1 cell line, showed the conjugates prepared in this study were more powerful in the reduction in tumor size and increasing the survival rate when compared to free docetaxel.

  16. Conjugation of transferrin to azide-modified CdSe/ZnS core-shell quantum dots using cyclooctyne click chemistry.

    Science.gov (United States)

    Schieber, Christine; Bestetti, Alessandra; Lim, Jet Phey; Ryan, Anneke D; Nguyen, Tich-Lam; Eldridge, Robert; White, Anthony R; Gleeson, Paul A; Donnelly, Paul S; Williams, Spencer J; Mulvaney, Paul

    2012-10-15

    Twinkle twinkle quantum dot: Conjugation of biomolecules to azide-modified quantum dots (QDs) through a bifunctional linker, using strain-promoted azide-alkyne cycloaddition with the QD and a squaramide linkage to the biomolecule (see scheme). Transferrin-conjugated QDs were internalized by transferrin-receptor expressing HeLa cells.

  17. Atomic Force Microscopy-based Cell Nanostructure for Ligand-conjugated Quantum Dot Endocytosis

    Institute of Scientific and Technical Information of China (English)

    Yun-Long PAN; Ji-Ye CAI; Li QIN; Hao WANG

    2006-01-01

    While it has been well demonstrated that quantum dots (QDs) play an important role in biological labeling both in vitro and in vivo,there is no report describing the cellular nanostructure basis of receptor-mediated endocytosis. Here, nanostructure evolution responses to the endocytosis of transferrin force microscopy (AFM). AFM-based nanostructure analysis demonstrated that the Tf-conjugated QDs were specifically and tightly bound to the cell receptors rrelated with the cell membrane receptor-mediated transduction.Consistently, confocal microscopic and flow cytometry results have demonstrated the specificity and the internalization of Tf-QD is linearly related to time. Moreover, while the nanoparticles on the cell membrane increased, the endocytosis was still nanoparticles did not interfere sterically with the binding and function of receptors. Therefore, ligand-conjugated QDs are potentially useful in biological labeling of cells at a nanometer scale.

  18. Double phase conjugation in tungsten bronze crystals.

    Science.gov (United States)

    Sharp, E J; Clark Iii, W W; Miller, M J; Wood, G L; Monson, B; Salamo, G J; Neurgaonkar, R R

    1990-02-20

    In this paper we report a new method for double phase conjugation particularly suited to the tungsten bronze crystal strontium barium niobate. It has also been observed to produce conjugate waves in BaTiO(3) and BSKNN. This new arrangement is called the bridge conjugator because the two beams enter opposing [100] crystal faces and fan together to form a bridge without reflection off a crystal face. Our measurements indicate that the bridge conjugator is competitive with previously reported double phase conjugate mirrors in reflectivity, response time, ease of alignment, and fidelity.

  19. DNA-templated antibody conjugation for targeted drug delivery to cancer cells

    DEFF Research Database (Denmark)

    Liu, Tianqiang

    2016-01-01

    -templated organic synthesis due to the wide existence of the 3-histidine cluster in most wild-type proteins. In this thesis, three projects that relate to targeted drug delivery to cancer cells based on the DTPC method is described. The first project was a delivery system which uses transferrin as the targeting...... ligand and saporin (ribosome inactivating protein) as the warhead to achieve enhanced cellular uptake and cytotoxicity of saporin to transferrin receptor overexpressed cancer cell line. The transferrin-saporin conjugate complex are formed by linking the site-selective DNA-transferrin conjugates with mono...... to cancer cells. The DNA duplex in the conjugates could be used for doxorubicin intercalation since it contains CGA repeats. Confocal microscopy and flow cytometry results showed a receptor-mediated targeting manner to EGFR+ cancer cell lines (KB and MDA-MB-231), and resulted in enhanced cell killing...

  20. Bazedoxifene and bazedoxifene combined with conjugated estrogens for the management of postmenopausal osteoporosis.

    Science.gov (United States)

    Lewiecki, E Michael

    2007-10-01

    Bazedoxifene acetate (WAY-140424; TSE-424) is an investigational non-steroidal indole-based selective estrogen receptor modulator (SERM) - also classified as an estrogen agonist/antagonist - that is being developed as a daily oral drug for the prevention and treatment of postmenopausal osteoporosis (PMO). Clinical studies have shown favorable effects on the skeleton, with prevention of bone loss in postmenopausal women without osteoporosis and reduction in vertebral fracture risk in women with PMO, without stimulation of endometrium or breast. Bazedoxifene combined with conjugated estrogens is an investigational tissue-selective estrogen complex, the first in a new class of therapeutic agents that pairs a selective estrogen receptor modulator with estrogens. Clinical trials with bazedoxifene/conjugated estrogens in postmenopausal women have shown skeletal benefit with improvement in menopausal vasomotor symptoms and little or no stimulation of endometrial or breast tissue. Bazedoxifene/conjugated estrogens is a potential agent for the prevention of PMO and control of menopausal symptoms.

  1. Conjugative plasmids of Neisseria gonorrhoeae.

    Directory of Open Access Journals (Sweden)

    Emilia Pachulec

    Full Text Available Many clinical isolates of the human pathogen Neisseria gonorrhoeae contain conjugative plasmids. The host range of these plasmids is limited to Neisseria species, but presence of a tetracycline (tetM determinant inserted in several of these plasmids is an important cause of the rapid spread of tetracycline resistance. Previously plasmids with different backbones (Dutch and American type backbones and with and without different tetM determinants (Dutch and American type tetM determinants have been identified. Within the isolates tested, all plasmids with American or Dutch type tetM determinants contained a Dutch type plasmid backbone. This demonstrated that tetM determinants should not be used to differentiate between conjugal plasmid backbones. The nucleotide sequences of conjugative plasmids with Dutch type plasmid backbones either not containing the tetM determinant (pEP5233 or containing Dutch (pEP5289 or American (pEP5050 type tetM determinants were determined. Analysis of the backbone sequences showed that they belong to a novel IncP1 subfamily divergent from the IncP1alpha, beta, gamma, delta and epsilon subfamilies. The tetM determinants were inserted in a genetic load region found in all these plasmids. Insertion was accompanied by the insertion of a gene with an unknown function, and rearrangement of a toxin/antitoxin gene cluster. The genetic load region contains two toxin/antitoxins of the Zeta/Epsilon toxin/antitoxin family previously only found in Gram positive organisms and the virulence associated protein D of the VapD/VapX toxin/antitoxin family. Remarkably, presence of VapX of pJD1, a small cryptic neisserial plasmid, in the acceptor strain strongly increased the conjugation efficiency, suggesting that it functions as an antitoxin for the conjugative plasmid. The presence of the toxin and antitoxin on different plasmids might explain why the host range of this IncP1 plasmid is limited to Neisseria species. The isolated plasmids

  2. Synthesis and evaluation of {sup 99m}Tc-labeled folate-tripeptide conjugate as a folate receptor-targeeted imaging agent in a tumor-bearing mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Myoung Hyoun; Kim, Chang Guhn; Kim, Dae Weung [Dept. of Nuclear Medicine, Wonkwang University School of Medicine, Iksan (Korea, Republic of); Kim, Woo Hyoung [Dept. of Nuclear Medicine, Seoul National University Hospital, Seoul (Korea, Republic of)

    2015-09-15

    The folate receptor (FR) is an attractive molecular target since it is overexpressed in a variety of human tumors. The purpose of the present study was to synthesize and evaluate the feasibility of a novel {sup 99m}Tc-ECG-EDA (Glu-Cys-Gly-ethylenediamine)-folate as an FR-positive tumor imaging agent in a mouse tumor model. ECG-EDA-folate was synthesized using solid phase peptide synthesis (SPPS) and radiolabeled with {sup 99m}Tc using tripeptide ECG as a chelator. FR-positive KB cells were inoculated in athymic nude mice. Following injection of {sup 99m}Tc-ECG-EDA-folate, serial scintigraphy and micro-SPECT/CT imaging were performed at various time points with and without pre-administration of excess free folate. Mean count densities (MCD) for regions of interest drawn on KB tumors and major normal organs at each time point were measured, and uptake ratios of tumor to normal organs were calculated. ECG-EDA-folate was labeled with {sup 99m}Tc with high radiolabeling efficiency and stability (>96 %). FR-positive tumors were clearly visualized on both scintigraphy and micro-SPECT/CT images and the tumor uptake of {sup 99m}Tc-ECG-EDA-folate was markedly suppressed with faint visualization of tumors by pre-administration of excess free folate on serial planar scintigraphy, indicating FR-specific binding of the agent. Furthermore, semiquantitative analysis of MCD data showed again that both tumor MCD and tumor-to-normal organ ratios decreased considerably by pre-administration of excess free folate, supporting FR-specific tumor uptake. Tumor-to-normal organ ratios approximately increased with time after injection until 4 h. The present study demonstrated that 9{sup 99m}Tc-ECG-EDA-folate can bind specifically to FR with clear visualization of FR-positive tumors in a mouse tumor model.

  3. Hyaluronic acid-serum albumin conjugate-based nanoparticles for targeted cancer therapy.

    Science.gov (United States)

    Edelman, Ravit; Assaraf, Yehuda G; Levitzky, Inna; Shahar, Tal; Livney, Yoav D

    2017-02-15

    Multiple carcinomas including breast, ovarian, colon, lung and stomach cancer, overexpress the hyaluronic acid (HA) receptor, CD44. Overexpression of CD44 contributes to key cancer processes including tumor invasion, metastasis, recurrence, and chemoresistance. Herein, we devised novel targeted nanoparticles (NPs) for delivery of anticancer chemotherapeutics, comprised of self-assembling Maillard reaction-based conjugates of HA and bovine serum albumin (BSA). HA served as the hydrophilic block, and as the ligand for actively targeting cancer cells overexpressing CD44. We demonstrate that Maillard reaction-based covalent conjugates of BSA-HA self-assemble into NPs, which efficiently entrap hydrophobic cytotoxic drugs including paclitaxel and imidazoacridinones. Furthermore, BSA-HA conjugates stabilized paclitaxel and prevented its aggregation and crystallization. The diameter of the NPs was < 15 nm, thus enabling CD44 receptor-mediated endocytosis. These NPs were selectively internalized by ovarian cancer cells overexpressing CD44, but not by cognate cells lacking this HA receptor. Moreover, free HA abolished the endocytosis of drug-loaded BSA-HA conjugates. Consistently, drug-loaded NPs were markedly more cytotoxic to cancer cells overexpressing CD44 than to cells lacking CD44, due to selective internalization, which could be competitively inhibited by excess free HA. Finally, a CD44-targeted antibody which blocks receptor activity, abolished internalization of drug-loaded NPs. In conclusion, a novel cytotoxic drug-loaded nanomedicine platform has been developed, which is based on natural biocompatible biopolymers, capabale of targeting cancer cells with functional surface expression of CD44.

  4. Fiber bundle phase conjugate mirror

    Science.gov (United States)

    Ward, Benjamin G.

    2012-05-01

    An improved method and apparatus for passively conjugating the phases of a distorted wavefronts resulting from optical phase mismatch between elements of a fiber laser array are disclosed. A method for passively conjugating a distorted wavefront comprises the steps of: multiplexing a plurality of probe fibers and a bundle pump fiber in a fiber bundle array; passing the multiplexed output from the fiber bundle array through a collimating lens and into one portion of a non-linear medium; passing the output from a pump collection fiber through a focusing lens and into another portion of the non-linear medium so that the output from the pump collection fiber mixes with the multiplexed output from the fiber bundle; adjusting one or more degrees of freedom of one or more of the fiber bundle array, the collimating lens, the focusing lens, the non-linear medium, or the pump collection fiber to produce a standing wave in the non-linear medium.

  5. Conjugated Polymers for Energy Production

    DEFF Research Database (Denmark)

    Livi, Francesco

    arylation (DAr) and direct arylation polymerization (DArP) have been applied to the preparation of PPDTBT, making this polymer readily available in only 4 synthetic steps and thus easily transferable to a large scale-production setup. DArP avoids organometallic species and therefore is an appealing......This dissertation is aimed at developing materials for flexible, large area, ITO-free polymer solar cells (PSCs) fully printed under ambient conditions. A large screening of conjugated polymers, both novel and well-known materials, has been carried out in order to find suitable candidates...... for scalable PSCs fully printed under ambient conditions [Adv. Energy Mater. 2015, 5, 1402186]. PPDTBT resulted to be the conjugated polymer with the best photovoltaic performance within the 104 synthesized macromolecules. Therefore, further studies have been done on such material. The impact of side chain...

  6. [{sup 99m}Tc(CO){sub 3}]{sup +}-(HE){sub 3}-Z{sub IGF1R:4551}, a new Affibody conjugate for visualization of insulin-like growth factor-1 receptor expression in malignant tumours

    Energy Technology Data Exchange (ETDEWEB)

    Orlova, Anna; Varasteh, Zohreh [Uppsala University, Preclinical PET Platform, Department of Medicinal Chemistry, Uppsala (Sweden); Hofstroem, Camilla; Graeslund, Torbjoern [Royal Institute of Technology, Division of Molecular Biotechnology, School of Biotechnology, Stockholm (Sweden); Strand, Joanna [Uppsala University, Division of Biomedical Radiation Sciences, Uppsala (Sweden); Sandstrom, Mattias [Uppsala University Hospital, Medical Physics, Department of Oncology, Uppsala (Sweden); Andersson, Karl [Uppsala University, Division of Biomedical Radiation Sciences, Uppsala (Sweden); Ridgeview Instruments AB, Uppsala (Sweden); Tolmachev, Vladimir [Uppsala University, Division of Biomedical Radiation Sciences, Uppsala (Sweden); Uppsala University, Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala (Sweden)

    2013-03-15

    Radionuclide imaging of insulin-like growth factor type 1 receptor (IGF-1R) expression in tumours might be used for selection of patients who would benefit from IGF-1R-targeted therapy. We have previously shown the feasibility of IGF-1R imaging using the Affibody molecule {sup 111}In-DOTA-His{sub 6}-Z{sub IGF1R:4551}. The use of {sup 99m}Tc instead of {sup 111}In should improve sensitivity and resolution of imaging, and reduce the dose burden to patients. We hypothesized that inclusion of a HEHEHE tag instead of a His{sub 6} tag in Z{sub IGF1R:4551} would permit its convenient purification using IMAC, enable labelling with [{sup 99m}Tc(CO){sub 3}]{sup +}, and improve its biodistribution. Z{sub IGF1R:4551} was expressed with a HEHEHE tag in the N terminus. The resulting (HE){sub 3}-Z{sub IGF1R:4551} construct was labelled with [{sup 99m}Tc(CO){sub 3}]{sup +}. Targeting of IGF-1R-expressing cells using [{sup 99m}Tc(CO){sub 3}]{sup +}-(HE){sub 3}-Z{sub IGF1R:4551} was evaluated in vitro and in vivo. (HE){sub 3}-Z{sub IGF1R:4551} was stably labelled with {sup 99m}Tc with preserved specific binding to IGF-1R-expressing DU-145 prostate cancer cells in vitro. In mice, [{sup 99m}Tc(CO){sub 3}]{sup +}-(HE){sub 3}-Z{sub IGF1R:4551} accumulated in IGF-1R-expressing organs (pancreas, stomach, lung and salivary gland). [{sup 99m}Tc(CO){sub 3}]{sup +}-(HE){sub 3}-Z{sub IGF1R:4551} demonstrated 3.6-fold lower accumulation in the liver and spleen than {sup 111}In-DOTA-Z{sub IGF1R:4551}. In NMRI nu/nu mice with DU-145 prostate cancer xenografts, the tumour uptake was 1.32 {+-} 0.11 %ID/g and the tumour-to-blood ratio was 4.4 {+-} 0.3 at 8 h after injection. The xenografts were visualized using a gamma camera 6 h after injection. [{sup 99m}Tc(CO){sub 3}]{sup +}-(HE){sub 3}-Z{sub IGF1R:4551} is a promising candidate for visualization of IGF-1R expression in malignant tumours. (orig.)

  7. Conjugated linoleic acid isomers and their precursor fatty acids regulate peroxisome proliferator-activated receptor subtypes and major peroxisome proliferator responsive element-bearing target genes in HepG2 cell model

    Institute of Scientific and Technical Information of China (English)

    Sailas BENJAMIN; Silke FLOTHO; Torsten B(O)RCHERS; Friedrich SPENER

    2013-01-01

    The purpose of this study was to examine the induction profiles(as judged by quantitative reverse transcription polymerase chain reaction(qRT-PCR))of peroxisome proliferator-activated receptor(PPAR)α,β,Y subtypes and major PPAR-target genes bearing a functional peroxisome proliferator responsive element(PPRE)in HepG2 cell model upon feeding with cis-9,trans-11-octadecadienoic acid(9-CLA)or trans-10,cis-12-octadecadienoic acid (10-CLA)or their precursor fatty acids(FAs).HepG2 cells were treated with 100 μmol/L 9-CLA or 10-CLA or their precursor FAs,viz.,oleic,linoleic,and trans-11-vaccenic acids against bezafibrate control to evaluate the induction/expression profiles of PPAR α,β,Y subtypes and major PPAR-target genes bearing a functional PPRE,i.e.,fatty acid transporter(FAT),glucose transporter-2(GLUT-2),liver-type FA binding protein(L-FABP),acyl CoA oxidase-1 (ACOX-1),and peroxisomal bifunctional enzyme(PBE)with reference to β-actin as house keeping gene.Of the three housekeeping genes(glyceraldehyde 3-phosphate dehydrogenase(GAPDH),β-actin,and ubiquitin),β-actin was found to be stable.Dimethyl sulfoxide(DMSO),the common solubilizer of agonists,showed a significantly higher induction of genes analyzed.qRT-PCR profiles of CLAs and their precursor FAs clearly showed upregulation of FAT,GLUT-2,and L-FABP(~0.5-2.0-fold).Compared to 10-CLA,9-CLA decreased the induction of the FA metabolizing gene ACOX-1 less than did PBE,while 10-CLA decreased the induction of PBE less than did ACOX-1.Both CLAs and precursor FAs upregulated PPRE-bearing genes,but with comparatively less or marginal activation of PPAR subtypes.This indicates that the binding of CLAs and their precursor FAs to PPAR subtypes results in PPAR activation,thereby induction of the target transporter genes coupled with downstream lipid metabolising genes such as ACOX-1 and PBE.To sum up,the expression profiles of these candidate genes showed that CLAs and their precursor FAs are involved in lipid

  8. Conjugated polyelectrolytes fundamentals and applications

    CERN Document Server

    Liu, Bin

    2013-01-01

    This is the first monograph to specifically focus on fundamentals and applications of polyelectrolytes, a class of molecules that gained substantial interest due to their unique combination of properties. Combining both features of organic semiconductors and polyelectrolytes, they offer a broad field for fundamental research as well as applications to analytical chemistry, optical imaging, and opto-electronic devices. The initial chapters introduce readers to the synthesis, optical and electrical properties of various conjugated polyelectrolytes. This is followed by chapters on the applica

  9. Labeling proteins with Tc-99m via hydrazinonicotinamide (HYNIC): optimization of the conjugation reaction

    Energy Technology Data Exchange (ETDEWEB)

    Rennen, Huub J.J.M. E-mail: H.Rennen@nugen.azn.nl; Boerman, Otto C.; Koenders, Emile B.; Oyen, Wim J.G.; Corstens, Frans H.M

    2000-06-01

    At present there is considerable interest in labeling peptides with Tc-99m for the development of target specific radiopharmaceuticals for imaging purposes. In the present study the conjugation of the bifunctional coupling agent succinimidyl-hydrazinonicotinamide (S-HYNIC) was studied and optimized in a series of peptides [molecular weight (MW) 6.5-14.3 kDa]. Aprotinin (MW 6.5 kDa), cytochrome C (MW 12.4 kDa), {alpha}-lactalbumin (MW 14.2 kDa), and lysozyme (MW 14.3 kDa) were conjugated with S- via the {epsilon} amino groups of their lysine residues. The effects of molar conjugation ratio, reaction temperature, pH, and protein concentration were studied. Reaction products were analyzed both with respect to the HYNIC-substitution ratio (spectrophotometrically) as well as to the labeling efficiency silica gel-instant thin layer chromatography (SG-ITLC) and molecular size fast performance liquid chromatography (FPLC). The effects of conjugation on biological activity were studied in three proteins binding to receptors on leukocytes: interleukin-8 (MW 8.5 kDa), interleukin-1{alpha} (MW 17 kDa), and interleukin-1 receptor antagonist (MW 17 kDa). The labeling efficiency of aprotinin, cytochrome c, {alpha}-lactalbumin, and lysozyme conjugated under optimal conjugation conditions exceeded 90%. Specific activities obtained were up to 7.5 MBq/{mu}g. Conjugation was most efficient at 0 deg. C (as compared to 20 and 40 deg. C), at pH 8.2 (as compared to 6.0, 7.2, and 9.5), and at protein concentrations {>=} 2.5 mg/mL. In general, efficiency increased with increasing molar conjugation ratio (protein-HYNIC-ratio 1:3 < 1:6 < 1:15 < 1:30). For the receptor binding proteins, biological activity was preserved only under the mildest conjugation conditions. For each of these proteins an inverse relation between labeling efficiency and receptor binding capacity was found. Labeling proteins with {sup 99m}Tc using S-HYNIC is easy, rapid, and efficient, and preparations with high specific

  10. A Conjugate Based on Anti-HER2 Diaffibody and Auristatin E Targets HER2-Positive Cancer Cells

    Science.gov (United States)

    Serwotka-Suszczak, Anna M.; Sochaj-Gregorczyk, Alicja M.; Pieczykolan, Jerzy; Krowarsch, Daniel; Jelen, Filip; Otlewski, Jacek

    2017-01-01

    Antibody-drug conjugates (ADCs) have recently emerged as efficient and selective cancer treatment therapeutics. Currently, alternative forms of drug carriers that can replace monoclonal antibodies are under intensive investigation. Here, a cytotoxic conjugate of an anti-HER2 (Human Epidermal Growth Factor Receptor 2) diaffibody with monomethyl-auristatin E (MMAE) is proposed as a potential anticancer therapeutic. The anti-HER2 diaffibody was based on the ZHER2:4 affibody amino acid sequence. The anti-HER2 diaffibody has been expressed as a His-tagged protein in E. coli and purified by Ni-nitrilotriacetyl (Ni-NTA) agarose chromatography. The molecule was properly folded, and the high affinity and specificity of its interaction with HER2 was confirmed by surface plasmon resonance (SPR) and flow cytometry, respectively. The (ZHER2:4)2DCS-MMAE conjugate was obtained by coupling the maleimide group linked with MMAE to cysteines, which were introduced in a drug conjugation sequence (DCS). Cytotoxicity of the conjugate was evaluated using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide MTT assay and the xCELLigence Real-Time Cell Analyzer. Our experiments demonstrated that the conjugate delivered auristatin E specifically to HER2-positive tumor cells, which finally led to their death. These results indicate that the cytotoxic diaffibody conjugate is a highly potent molecule for the treatment of various types of cancer overexpressing HER2 receptors. PMID:28216573

  11. Peptide-conjugated micelles as a targeting nanocarrier for gene delivery

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Wen Jen, E-mail: wjlin@ntu.edu.tw; Chien, Wei Hsuan [National Taiwan University, School of Pharmacy, Graduate Institute of Pharmaceutical Sciences (China)

    2015-09-15

    The aim of this study was to develop peptide-conjugated micelles possessing epidermal growth factor receptor (EGFR) targeting ability for gene delivery. A sequence-modified dodecylpeptide, GE11(2R), with enhancing EGF receptor binding affinity, was applied in this study as a targeting ligand. The active targeting micelles were composed of poly(d,l-lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) copolymer conjugated with GE11(2R)-peptide. The particle sizes of peptide-free and peptide-conjugated micelles were 277.0 ± 5.1 and 308.7 ± 14.5 nm, respectively. The peptide-conjugated micelles demonstrated the cellular uptake significantly higher than peptide-free micelles in EGFR high-expressed MDA-MB-231 and MDA-MB-468 cells due to GE11(2R)-peptide specificity. Furthermore, the peptide-conjugated micelles were able to encapsulate plasmid DNA and expressed cellular transfection higher than peptide-free micelles in EGFR high-expressed cells. The EGFR-targeting delivery micelles enhanced DNA internalized into cells and achieved higher cellular transfection in EGFR high-expressed cells.

  12. Hepatocyte-specific delivery of siRNAs conjugated to novel non-nucleosidic trivalent N-acetylgalactosamine elicits robust gene silencing in vivo.

    Science.gov (United States)

    Rajeev, Kallanthottathil G; Nair, Jayaprakash K; Jayaraman, Muthusamy; Charisse, Klaus; Taneja, Nate; O'Shea, Jonathan; Willoughby, Jennifer L S; Yucius, Kristina; Nguyen, Tuyen; Shulga-Morskaya, Svetlana; Milstein, Stuart; Liebow, Abigail; Querbes, William; Borodovsky, Anna; Fitzgerald, Kevin; Maier, Martin A; Manoharan, Muthiah

    2015-04-13

    We recently demonstrated that siRNAs conjugated to triantennary N-acetylgalactosamine (GalNAc) induce robust RNAi-mediated gene silencing in the liver, owing to uptake mediated by the asialoglycoprotein receptor (ASGPR). Novel monovalent GalNAc units, based on a non-nucleosidic linker, were developed to yield simplified trivalent GalNAc-conjugated oligonucleotides under solid-phase synthesis conditions. Synthesis of oligonucleotide conjugates using monovalent GalNAc building blocks required fewer synthetic steps compared to the previously optimized triantennary GalNAc construct. The redesigned trivalent GalNAc ligand maintained optimal valency, spatial orientation, and distance between the sugar moieties for proper recognition by ASGPR. siRNA conjugates were synthesized by sequential covalent attachment of the trivalent GalNAc to the 3'-end of the sense strand and resulted in a conjugate with in vitro and in vivo potency similar to that of the parent trivalent GalNAc conjugate design.

  13. Modelling conjugation with stochastic differential equations.

    Science.gov (United States)

    Philipsen, K R; Christiansen, L E; Hasman, H; Madsen, H

    2010-03-07

    Conjugation is an important mechanism involved in the transfer of resistance between bacteria. In this article a stochastic differential equation based model consisting of a continuous time state equation and a discrete time measurement equation is introduced to model growth and conjugation of two Enterococcus faecium strains in a rich exhaustible media. The model contains a new expression for a substrate dependent conjugation rate. A maximum likelihood based method is used to estimate the model parameters. Different models including different noise structure for the system and observations are compared using a likelihood-ratio test and Akaike's information criterion. Experiments indicating conjugation on the agar plates selecting for transconjugants motivates the introduction of an extended model, for which conjugation on the agar plate is described in the measurement equation. This model is compared to the model without plate conjugation. The modelling approach described in this article can be applied generally when modelling dynamical systems.

  14. Linker-free conjugation and specific cell targeting of antibody functionalized iron-oxide nanoparticles

    Science.gov (United States)

    Xu, Yaolin; Baiu, Dana C.; Sherwood, Jennifer A.; McElreath, Meghan R.; Qin, Ying; Lackey, Kimberly H.; Otto, Mario; Bao, Yuping

    2015-01-01

    Specific targeting is a key step to realize the full potential of iron oxide nanoparticles in biomedical applications, especially tumor-associated diagnosis and therapy. Here, we developed anti-GD2 antibody conjugated iron oxide nanoparticles for highly efficient neuroblastoma cell targeting. The antibody conjugation was achieved through an easy, linker-free method based on catechol reactions. The targeting efficiency and specificity of the antibody-conjugated nanoparticles to GD2-positive neuroblastoma cells were confirmed by flow cytometry, fluorescence microscopy, Prussian blue staining and transmission electron microscopy. These detailed studies indicated that the receptor-recognition capability of the antibody was fully retained after conjugation and the conjugated nanoparticles quickly attached to GD2-positive cells within four hours. Interestingly, longer treatment (12 h) led the cell membrane-bound nanoparticles to be internalized into cytosol, either by directly penetrating the cell membrane or escaping from the endosomes. Last but importantly, the uniquely designed functional surfaces of the nanoparticles allow easy conjugation of other bioactive molecules. PMID:26660881

  15. Easy and Efficient 111Indium Labeling of Long-Term Stored DTPA Conjugated Protein

    DEFF Research Database (Denmark)

    Nalla, Amarnadh; Buch, Inge; Hesse, Birger

    2011-01-01

    The labelling efficiency of long-term stored DTPA-conjugates has not been reported previously even though DTPA has been in extensive use as metal chelator in the development of radiopharmaceuticals and contrast agents. DTPA is often used as a bifunctional chelating agent conjugated to tumor...... targeting vehicles such as monoclonal antibodies and receptor directed peptides. The purpose of this study was to monitor the labelling efficiency of a DTPA-conjugate on long-term storage using 111In-chloride at two different temperatures and incubation times for the In-labelling. Method: Cyclic......-diethylene-triamine-pentaacetic acid (cDTAP) was conjugated to a polyclonal immunoglobulin-G (IgG) in borate buffer, pH 8.2 at +4?C for 4 hours. Then the DTPA-conjugate was dialyzed against 50 mmol/l sodium citrate buffer saline, pH 6.0 and stored at -80° C in aliquots of 1 mg/0.5 ml. The DTPA-conjugate was labeled with 111In...

  16. Cysteine S-conjugate β-lyases

    OpenAIRE

    Arthur J. L. Cooper; Krasnikov, Boris F.; Pinto, John T.; Bruschi, Sam A.

    2010-01-01

    Cysteine S-conjugate β-lyases are pyridoxal 5′-phosphate (PLP)-containing enzymes that catalyze the conversion of cysteine S-conjugates [RSCH2CH(NH3+)CO2−] and selenium Se-conjugates [RSeCH2CH(NH3+)CO2−] that contain a leaving group in the β position to pyruvate, ammonium and a sulfur-containing fragment (RSH) or selenium-containing fragment (RSeH), respectively. At least ten PLP enzymes catalyze β-elimination reactions with such cysteine S-conjugates. All are enzymes involved in amino acid m...

  17. The Tcp conjugation system of Clostridium perfringens.

    Science.gov (United States)

    Wisniewski, Jessica A; Rood, Julian I

    2017-03-07

    The Gram-positive pathogen Clostridium perfringens possesses a family of large conjugative plasmids that is typified by the tetracycline resistance plasmid pCW3. Since these plasmids may carry antibiotic resistance genes or genes encoding extracellular or sporulation-associated toxins, the conjugative transfer of these plasmids appears to be important for the epidemiology of C. perfringens-mediated diseases. Sequence analysis of members of this plasmid family identified a highly conserved 35kb region that encodes proteins with various functions, including plasmid replication and partitioning. The tcp conjugation locus also was identified in this region, initially based on low-level amino acid sequence identity to conjugation proteins from the integrative conjugative element Tn916. Genetic studies confirmed that the tcp locus is required for conjugative transfer and combined with biochemical and structural analyses have led to the development of a functional model of the Tcp conjugation apparatus. This review summarises our current understanding of the Tcp conjugation system, which is now one of the best-characterized conjugation systems in Gram-positive bacteria.

  18. Modelling conjugation with stochastic differential equations

    DEFF Research Database (Denmark)

    Philipsen, Kirsten Riber; Christiansen, Lasse Engbo; Hasman, Henrik

    2010-01-01

    Conjugation is an important mechanism involved in the transfer of resistance between bacteria. In this article a stochastic differential equation based model consisting of a continuous time state equation and a discrete time measurement equation is introduced to model growth and conjugation of two...... using a likelihood-ratio test and Akaike's information criterion. Experiments indicating conjugation on the agar plates selecting for transconjugants motivates the introduction of an extended model, for which conjugation on the agar plate is described in the measurement equation. This model is compared...

  19. Design, automated synthesis and immunological evaluation of NOD2-ligand–antigen conjugates

    Directory of Open Access Journals (Sweden)

    Marian M. J. H. P. Willems

    2014-06-01

    Full Text Available The covalent attachment of an innate immune system stimulating agent to an antigen can provide active vaccine modalities capable of eliciting a potent immune response against the incorporated antigen. Here we describe the design, automated synthesis and immunological evaluation of a set of four muramyl dipeptide–peptide antigen conjugates. Muramyl dipeptide (MDP represents a well-known ligand for the intracellular NOD2 receptor and our study shows that covalently linking an MDP-moiety to an antigenic peptide can lead to a construct that is capable of stimulating the NOD2 receptor if the ligand is attached at the anomeric center of the muramic acid. The constructs can be processed by dendritic cells (DCs and the conjugation does not adversely affect the presentation of the incorporated SIINFEKL epitope on MHC-I molecules. However, stimulation of the NOD2 receptor in DCs was not sufficient to provide a strong immunostimulatory signal.

  20. Test of charge conjugation invariance.

    Science.gov (United States)

    Nefkens, B M K; Prakhov, S; Gårdestig, A; Allgower, C E; Bekrenev, V; Briscoe, W J; Clajus, M; Comfort, J R; Craig, K; Grosnick, D; Isenhower, D; Knecht, N; Koetke, D; Koulbardis, A; Kozlenko, N; Kruglov, S; Lolos, G; Lopatin, I; Manley, D M; Manweiler, R; Marusić, A; McDonald, S; Olmsted, J; Papandreou, Z; Peaslee, D; Phaisangittisakul, N; Price, J W; Ramirez, A F; Sadler, M; Shafi, A; Spinka, H; Stanislaus, T D S; Starostin, A; Staudenmaier, H M; Supek, I; Tippens, W B

    2005-02-04

    We report on the first determination of upper limits on the branching ratio (BR) of eta decay to pi0pi0gamma and to pi0pi0pi0gamma. Both decay modes are strictly forbidden by charge conjugation (C) invariance. Using the Crystal Ball multiphoton detector, we obtained BR(eta-->pi0pi0gamma)pi0pi0pi0gamma)<6 x 10(-5) at the 90% confidence level, in support of C invariance of isovector electromagnetic interactions.

  1. Waveguide mutually pumped phase conjugators

    OpenAIRE

    James, S. W.; Youden, K.E.; Jeffrey, P. M.; EASON, R. W.; Chandler, P.J.; Zhang, L.; Townsend, P.D.

    1993-01-01

    The operation of the Bridge Mutually Pumped Phase Conjugator is reported in a planar waveguide structure in photorefractive BaTiO3. The waveguide was fabricated by the technique of ion implantation. using 1.5 MeV H+ at a dose of 10^16 ions/cm^2. An order of magnitude decrease in response time is observed in the waveguide as compared to typical values obtained in bulk crystals, probably resulting from a combination of the optical confinement within the waveguide, and possibly modification of t...

  2. Short Conjugators in Solvable Groups

    CERN Document Server

    Sale, Andrew W

    2011-01-01

    We give an upper bound on the size of short conjugators in certain solvable groups. Diestel-Leader graphs, which are a horocyclic product of trees, are discussed briefly and used to study the lamplighter groups. The other solvable groups we look at can be recognised in a similar vein, as groups which act on a horocyclic product of well known spaces. These include the Baumslag-Solitar groups BS(1,q) and semidirect products of Z^n with Z^k. Results can also be applied to the conjugacy of parabolic elements in Hilbert modular groups and to elements in 3-manifold groups.

  3. RGD-conjugated albumin nanoparticles as a novel delivery vehicle in pancreatic cancer therapy.

    Science.gov (United States)

    Ji, Shunrong; Xu, Jin; Zhang, Bo; Yao, Wantong; Xu, Wenyan; Wu, Wenzhe; Xu, Yongfeng; Wang, Hao; Ni, Quanxing; Hou, Huimin; Yu, Xianjun

    2012-02-15

    Integrin αvβ3 receptor is expressed on several types of cancer cells, including pancreatic cancer cells, and plays an important role in tumor growth and metastasis. The ability to target the integrin αvβ3 receptor on cancer cells increases the efficacy of targeted therapy and reduces the side effects. The aim of this study is to develop a novel arginine-glycine-aspartic acid (RGD) peptide -conjugated albumin nanoparticle to enhance the intracellular uptake of anticancer drug into the pancreatic cancer cells through receptor-mediated endocytosis. In the cellular uptake studies, the fluorescent signal of RGD-conjugated BSANPs in BxPC3 cells was higher than that of BSANPs without RGD conjugation as determined by fluorescence spectrophotometer. We also found that BSANPs bound to BxPC3 cells in a time- and concentration-dependent manner. The uptake of RGD-conjugated BSANPs by pancreatic cancer cells was inhibited by an excess amount of free RGD peptide, indicating that the binding and/or uptake were mediated by the αvβ3 receptor. Furthermore, the nanoparticles were found to be located close to the nuclei by using laser scanning confocal microscopy. Besides, no significant in vitro cytotoxicity was observed as measured with MTT assay. Both in vitro and in vivo antitumor efficacy was improved by targeting gemcitabine-loaded nanoparticles to BxPC-3 cells using RGD peptides. Therefore, the RGD-conjugated BSANPs hold great potential as an effective drug delivery system to deliver therapeutic agents to pancreatic cancer.

  4. Photoluminescence of Conjugated Star Polymers

    Science.gov (United States)

    Ferguson, J. B.; Prigodin, N. V.; Epstein, A. J.; Wang, F.

    2000-10-01

    Higher dimensionality "star" polymers provide new properties beyond those found in their linear analogs. They have been used to improving electronic properties for nonlinear optics through exciton transfer and molecular antenna structures for example (M. Kawa, J. M. J. Frechet, Chem. Mater. 10, 286 (1998).). We report on photoluminescence properties of star polymers with a hyperbranched core (both hyperbranched phenlyene and hyperbranched triphenylamine) and polyhexylthiophene arms. The arm is a conjugated oligomer of polythiophene that has been investigated extensively for metallic like conductivity when doped as well as utilized in field effect transistors in its undoped form (A. Tsumara, H. Koezuka, T. Ando, Appl. Phys. Lett. 49, 1210 (1986).). The cores are respectively, a nonconjugated polymer in the case of hyperbranched phenlyene and a conjugated polymer in the case of hyperbranched triphenylamine. The photoluminesce spectrum (λ_max at 575 nm) is identical for both star polymers with the two electronically different hyperbranched cores and for linear polythiophene alone. We conclude the wave functions of the core and arms do not strongly interact to form states different from their individual states and excitons formed on the hyperbranched cores migrate to the lower bandgap polythiophene before recombining.

  5. Subgap Absorption in Conjugated Polymers

    Science.gov (United States)

    Sinclair, M.; Seager, C. H.; McBranch, D.; Heeger, A. J; Baker, G. L.

    1991-01-01

    Along with X{sup (3)}, the magnitude of the optical absorption in the transparent window below the principal absorption edge is an important parameter which will ultimately determine the utility of conjugated polymers in active integrated optical devices. With an absorptance sensitivity of conjugated polymers poly(1,4-phenylene-vinylene) (and derivitives) and polydiacetylene-4BCMU in the spectral region from 0.55 eV to 3 eV. Our spectra show that the shape of the absorption edge varies considerably from polymer to polymer, with polydiacetylene-4BCMU having the steepest absorption edge. The minimum absorption coefficients measured varied somewhat with sample age and quality, but were typically in the range 1 cm{sup {minus}1} to 10 cm{sup {minus}1}. In the region below 1 eV, overtones of C-H stretching modes were observed, indicating that further improvements in transparency in this spectral region might be achieved via deuteration of fluorination.

  6. The Conjugate Acid-Base Chart.

    Science.gov (United States)

    Treptow, Richard S.

    1986-01-01

    Discusses the difficulties that beginning chemistry students have in understanding acid-base chemistry. Describes the use of conjugate acid-base charts in helping students visualize the conjugate relationship. Addresses chart construction, metal ions, buffers and pH titrations, and the organic functional groups and nonaqueous solvents. (TW)

  7. DENDRIMER CONJUGATES FOR SELECTIVE OF PROTEIN AGGREGATES

    DEFF Research Database (Denmark)

    2004-01-01

    Dendrimer conjugates are presented, which are formed between a dendrimer and a protein solubilising substance. Such dendrimer conjugates are effective in the treatment of protein aggregate-related diseases (e.g. prion-related diseases). The protein solubilising substance and the dendrimer together...

  8. CONJUGATED BLOCK-COPOLYMERS FOR ELECTROLUMINESCENT DIODES

    NARCIS (Netherlands)

    Hilberer, A; Gill, R.E; Herrema, J.K; Malliaras, G.G; Wildeman, J.; Hadziioannou, G

    1995-01-01

    In this article we review results obtained in our laboratory on the design and study of new light-emitting polymers. We are interested in the synthesis and characterisation of block copolymers with regularly alternating conjugated and non conjugated sequences. The blocks giving rise to luminescence

  9. Bio-Conjugates for Nanoscale Applications

    DEFF Research Database (Denmark)

    Villadsen, Klaus

    Bio-conjugates for Nanoscale Applications is the title of this thesis, which covers three different projects in chemical bio-conjugation research, namely synthesis and applications of: Lipidated fluorescent peptides, carbohydrate oxime-azide linkers and N-aryl O-R2 oxyamine derivatives. Lipidated...

  10. CONJUGATED BLOCK-COPOLYMERS FOR ELECTROLUMINESCENT DIODES

    NARCIS (Netherlands)

    Hilberer, A; Gill, R.E; Herrema, J.K; Malliaras, G.G; Wildeman, J.; Hadziioannou, G

    1995-01-01

    In this article we review results obtained in our laboratory on the design and study of new light-emitting polymers. We are interested in the synthesis and characterisation of block copolymers with regularly alternating conjugated and non conjugated sequences. The blocks giving rise to luminescence

  11. CONJUGATE-SYMPLECTICITY OF LINEAR MULTISTEP METHODS

    Institute of Scientific and Technical Information of China (English)

    Ernst Hairer

    2008-01-01

    For the numerical treatment of Hamiltonian differential equations, symplectic integra-tors are the most suitable choice, and methods that are conjugate to a symplectic integrator share the same good long-time behavior. This note characterizes linear multistep methods whose underlying one-step method is conjugate to a symplectic integrator. The bounded-hess of parasitic solution components is not addressed.

  12. Kinetic models of conjugated metabolic cycles

    Science.gov (United States)

    Ershov, Yu. A.

    2016-01-01

    A general method is developed for the quantitative kinetic analysis of conjugated metabolic cycles in the human organism. This method is used as a basis for constructing a kinetic graph and model of the conjugated citric acid and ureapoiesis cycles. The results from a kinetic analysis of the model for these cycles are given.

  13. Bio-Conjugates for Nanoscale Applications

    DEFF Research Database (Denmark)

    Villadsen, Klaus

    Bio-conjugates for Nanoscale Applications is the title of this thesis, which covers three different projects in chemical bio-conjugation research, namely synthesis and applications of: Lipidated fluorescent peptides, carbohydrate oxime-azide linkers and N-aryl O-R2 oxyamine derivatives. Lipidated...

  14. LEDs based on conjugated PPV block copolymers

    NARCIS (Netherlands)

    Brouwer, H.J.; Hilberer, A.; Krasnikov, V.V.; Werts, M.; Wildeman, J.; Hadziioannou, G.

    1997-01-01

    A way to control the bandgap in semi-conducting polymers is by preparing polymers with a partially conjugated backbone. In our laboratory, three conjugated copolymers containing PPV trimers as light emitting chromophores have been synthesized, which emit in the blue, green and orange wavelength regi

  15. A new family of conjugate gradient methods

    Science.gov (United States)

    Shi, Zhen-Jun; Guo, Jinhua

    2009-02-01

    In this paper we develop a new class of conjugate gradient methods for unconstrained optimization problems. A new nonmonotone line search technique is proposed to guarantee the global convergence of these conjugate gradient methods under some mild conditions. In particular, Polak-Ribiére-Polyak and Liu-Storey conjugate gradient methods are special cases of the new class of conjugate gradient methods. By estimating the local Lipschitz constant of the derivative of objective functions, we can find an adequate step size and substantially decrease the function evaluations at each iteration. Numerical results show that these new conjugate gradient methods are effective in minimizing large-scale non-convex non-quadratic functions.

  16. Energetic Tuning in Spirocyclic Conjugated Polymers

    Directory of Open Access Journals (Sweden)

    Hugo Bronstein

    2016-01-01

    Full Text Available Precise control of the energy levels in a conjugated polymer is the key to allowing their exploitation in optoelectronic devices. The introduction of spirocycles into conjugated polymers has traditionally been used to enhance their solid state microstructure. Here we present a highly novel method of energetic tuning through the use of electronically active spirocyclic systems. By modifying the size and oxidation state of a heteroatom in an orthogonal spirocycle we demonstrate energetic fine tuning in both the absorption and emission of a conjugated polymer. Furthermore, the synthesis of highly novel triplet-decker spirocyclic conjugated polymers is presented. This new method of energetic manipulation in a conjugated polymer paves the way for future application targeted synthesis of polymers with electronically active spirocycles.

  17. Integrin Targeting and Toxicological Assessment of Peptide-Conjugated Liposome Delivery Systems to Activated Endothelial Cells

    DEFF Research Database (Denmark)

    Kermanizadeh, Ali; Villadsen, Klaus; Østrem, Ragnhild Garborg

    2017-01-01

    Utilisation of functionalized liposomes as the means of targeted delivery of therapeutics may enhance specific transport of biologically active drugs to target tissues, while avoiding or reducing undesired side effects. In the present investigation, peptide-conjugated cationic liposomes were cons....... Therefore, this study demonstrates the feasibility of constructing a peptide-conjugated cationic liposome, which displays targeting to activated endothelial cells at concentrations that are not cytotoxic or inflammogenic to the cells....... constructed with the aim of targeting integrins (i.e. vitronectin and/or fibronectin receptors) on activated endothelial cells. The peptide-conjugated liposomes induced only cytotoxicity at the highest concentration in non-activated or activated endothelial cells, as well as in co-culture of endothelial cells...

  18. Photoconductive properties of conjugated polymers

    CERN Document Server

    Halls, J J M

    1997-01-01

    The research described in my dissertation has involved the fabrication and characterisation of photovoltaic cells based on conjugated polymers, including the widely studied polymer poly(p-phenylenevinylene). These materials have semiconducting properties which arise from the delocalisation of electrons along the pi-electron systems of the polymer chains. Research into these materials is motivated both by their novel electronic properties, and also their potential for use in a wide range of applications including light-emitting diodes (LEDs), thin-film transistors, and photovoltaic cells (solar cells and light detectors). Light absorbed in a photovoltaic cell generates opposite charges which are collected at two different electrodes, giving rise to an electric current

  19. Test of Charge Conjugation Invariance

    Science.gov (United States)

    Nefkens, B. M.; Prakhov, S.; Gårdestig, A.; Allgower, C. E.; Bekrenev, V.; Briscoe, W. J.; Clajus, M.; Comfort, J. R.; Craig, K.; Grosnick, D.; Isenhower, D.; Knecht, N.; Koetke, D.; Koulbardis, A.; Kozlenko, N.; Kruglov, S.; Lolos, G.; Lopatin, I.; Manley, D. M.; Manweiler, R.; Marušić, A.; McDonald, S.; Olmsted, J.; Papandreou, Z.; Peaslee, D.; Phaisangittisakul, N.; Price, J. W.; Ramirez, A. F.; Sadler, M.; Shafi, A.; Spinka, H.; Stanislaus, T. D.; Starostin, A.; Staudenmaier, H. M.; Supek, I.; Tippens, W. B.

    2005-02-01

    We report on the first determination of upper limits on the branching ratio (BR) of η decay to π0π0γ and to π0π0π0γ. Both decay modes are strictly forbidden by charge conjugation (C) invariance. Using the Crystal Ball multiphoton detector, we obtained BR(η→π0π0γ)<5×10-4 at the 90% confidence level, in support of C invariance of isoscalar electromagnetic interactions of the light quarks. We have also measured BR(η→π0π0π0γ)<6×10-5 at the 90% confidence level, in support of C invariance of isovector electromagnetic interactions.

  20. Peptide-LNA oligonucleotide conjugates

    DEFF Research Database (Denmark)

    Astakhova, I Kira; Hansen, Lykke Haastrup; Vester, Birte

    2013-01-01

    properties, peptides were introduced into oligonucleotides via a 2'-alkyne-2'-amino-LNA scaffold. Derivatives of methionine- and leucine-enkephalins were chosen as model peptides of mixed amino acid content, which were singly and doubly incorporated into LNA/DNA strands using highly efficient copper......Although peptide-oligonucleotide conjugates (POCs) are well-known for nucleic acids delivery and therapy, reports on internal attachment of peptides to oligonucleotides are limited in number. To develop a convenient route for preparation of internally labeled POCs with improved biomedical......(i)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" chemistry. DNA/RNA target binding affinity and selectivity of the resulting POCs were improved in comparison to LNA/DNA mixmers and unmodified DNA controls. This clearly demonstrates that internal attachment of peptides to oligonucleotides can significantly...

  1. Enhancement of gene transfer activity mediated by mannosylated dendrimer/alpha-cyclodextrin conjugate (generation 3, G3).

    Science.gov (United States)

    Arima, Hidetoshi; Chihara, Yuko; Arizono, Masayo; Yamashita, Shogo; Wada, Koki; Hirayama, Fumitoshi; Uekama, Kaneto

    2006-11-01

    To enhance gene transfer activity of dendrimers, we prepared its conjugate (generation 3, G3) with alpha-cyclodextrin bearing mannose (Man-alpha-CDE conjugates) with various degrees of substitution of the mannose moiety (DSM5, 10, 13, 20) and compared their cytotoxicity and gene transfer activity, and elucidated the enhancing mechanism for the activity. Of the various carriers used here, Man-alpha-CDE conjugate (G3, DSM10) provided the highest gene transfer activity in NR8383, A549, NIH3T3 and HepG2 cells, being independent of the expression of mannose receptors. Gene transfer activity of Man-alpha-CDE conjugate (G3, DSM10) was not decreased by the addition of 10% serum in A549 cells. Cytotoxicity of the polyplex with Man-alpha-CDE conjugates (G3, DSM10) was not observed in A549 and NIH3T3 cells up to the charge ratio of 200/1 (carrier/pDNA). The gel mobility and particle size of polyplex with Man-alpha-CDE conjugate (G3, DSM10) were relevant to those with alpha-CDE conjugate (G3), but zeta-potential, DNase I stability, pDNA condensation of the former polyplex were somewhat different from those of the latter one. Cellular association of polyplex with Man-alpha-CDE conjugate (G3, DSM10) was almost comparable to that with dendrimer (G3) complex and alpha-CDE conjugate (G3). The addition of mannan and mannose attenuated gene transfer activity of Man-alpha-CDE conjugate (G3, DSM10) in A549 cells. Alexa-pDNA complex with TRITC-Man-alpha-CDE conjugate (G3, DSM10), but not the complex with TRITC-alpha-CDE conjugate (G3), was found to translocate to nucleus at 24 h after incubation in A549 cells. HVJ-E vector including mannan, but neither the vector alone nor the vector including dextran, suppressed the nuclear localization of TRITC-Man-alpha-CDE conjugate (G3, DSM10) to a striking degree after 24 h incubation in A549 cells. These results suggest that Man-alpha-CDE conjugate (G3, DSM10) has less cytotoxicity and prominent gene transfer activity through not only its serum

  2. Sensitization of spinal cord nociceptive neurons with a conjugate of substance P and cholera toxin

    Directory of Open Access Journals (Sweden)

    Perez Federico M

    2007-05-01

    Full Text Available Abstract Background Several investigators have coupled toxins to neuropeptides for the purpose of lesioning specific neurons in the central nervous system. By producing deficits in function these toxin conjugates have yielded valuable information about the role of these cells. In an effort to specifically stimulate cells rather than kill them we have conjugated the neuropeptide substance P to the catalytic subunit of cholera toxin (SP-CTA. This conjugate should be taken up selectively by neurokinin receptor expressing neurons resulting in enhanced adenylate cyclase activity and neuronal firing. Results The conjugate SP-CTA stimulates adenylate cyclase in cultured cells that are transfected with either the NK1 or NK2 receptor, but not the NK3 receptor. We further demonstrate that intrathecal injection of SP-CTA in rats induces the phosphorylation of the transcription factor cyclic AMP response element binding protein (CREB and also enhances the expression of the immediate early gene c-Fos. Behaviorally, low doses of SP-CTA (1 μg injected intrathecally produce thermal hyperalgesia. At higher doses (10 μg peripheral sensitivity is suppressed suggesting that descending inhibitory pathways may be activated by the SP-CTA induced sensitization of spinal cord neurons. Conclusion The finding that stimulation of adenylate cyclase in neurokinin receptor expressing neurons in the spinal cord produces thermal hyperalgesia is consistent with the known actions of these neurons. These data demonstrate that cholera toxin can be targeted to specific cell types by coupling the catalytic subunit to a peptide agonist for a g-protein coupled receptor. Furthermore, these results demonstrate that SP-CTA can be used as a tool to study sensitization of central neurons in vivo in the absence of an injury.

  3. Inhibition of bacterial conjugation by phage M13 and its protein g3p: quantitative analysis and model.

    Directory of Open Access Journals (Sweden)

    Abraham Lin

    Full Text Available Conjugation is the main mode of horizontal gene transfer that spreads antibiotic resistance among bacteria. Strategies for inhibiting conjugation may be useful for preserving the effectiveness of antibiotics and preventing the emergence of bacterial strains with multiple resistances. Filamentous bacteriophages were first observed to inhibit conjugation several decades ago. Here we investigate the mechanism of inhibition and find that the primary effect on conjugation is occlusion of the conjugative pilus by phage particles. This interaction is mediated primarily by phage coat protein g3p, and exogenous addition of the soluble fragment of g3p inhibited conjugation at low nanomolar concentrations. Our data are quantitatively consistent with a simple model in which association between the pili and phage particles or g3p prevents transmission of an F plasmid encoding tetracycline resistance. We also observe a decrease in the donor ability of infected cells, which is quantitatively consistent with a reduction in pili elaboration. Since many antibiotic-resistance factors confer susceptibility to phage infection through expression of conjugative pili (the receptor for filamentous phage, these results suggest that phage may be a source of soluble proteins that slow the spread of antibiotic resistance genes.

  4. Reduction-sensitive liposomes from a multifunctional lipid conjugate and natural phospholipids: reduction and release kinetics and cellular uptake.

    Science.gov (United States)

    Goldenbogen, Björn; Brodersen, Nicolai; Gramatica, Andrea; Loew, Martin; Liebscher, Jürgen; Herrmann, Andreas; Egger, Holger; Budde, Bastian; Arbuzova, Anna

    2011-09-06

    The development of targeted and triggerable delivery systems is of high relevance for anticancer therapies. We report here on reduction-sensitive liposomes composed of a novel multifunctional lipidlike conjugate, containing a disulfide bond and a biotin moiety, and natural phospholipids. The incorporation of the disulfide conjugate into vesicles and the kinetics of their reduction were studied using dansyl-labeled conjugate 1 in using the dansyl fluorescence environmental sensitivity and the Förster resonance energy transfer from dansyl to rhodamine-labeled phospholipids. Cleavage of the disulfide bridge (e.g., by tris(2-carboxyethyl)phosphine (TCEP), dithiothreitol (DTT), l-cysteine, or glutathione (GSH)) removed the hydrophilic headgroup of the conjugate and thus changed the membrane organization leading to the release of entrapped molecules. Upon nonspecific uptake of vesicles by macrophages, calcein release from reduction-sensitive liposomes consisting of the disulfide conjugate and phospholipids was more efficient than from reduction-insensitive liposomes composed only of phospholipids. The binding of streptavidin to the conjugates did not interfere with either the subsequent reduction of the disulfide bond of the conjugate or the release of entrapped molecules. Breast cancer cell line BT-474, overexpressing the HER2 receptor, showed a high uptake of the reduction-sensitive doxorubicin-loaded liposomes functionalized with the biotin-tagged anti-HER2 antibody. The release of the entrapped cargo inside the cells was observed, implying the potential of using our system for active targeting and delivery. © 2011 American Chemical Society

  5. R-phycoerythrin-conjugated antibodies are inappropriate for intracellular staining of murine plasma cells.

    Science.gov (United States)

    Kim, Myun Soo; Kim, Tae Sung

    2013-05-01

    Phycoerythrin (PE) is a type of phycobiliproteins found in cyanobacteria and red algae. PE-conjugated antibodies are broadly used for flow cytometry and immunofluorescence microscopy. Because nonspecific binding of antibodies results in decreased analytic accuracy, numerous efforts have been made to unveil cases and mechanisms of nonspecific bindings. However, nonspecific binding of specific cell types by a fluorescent dye-conjugated form of antibody has been rarely reported. In the present study, we discovered that PE-conjugated antibodies, but not FITC- or APC-antibodies, selectively stained lamina propria plasma cells (LP-PCs) from the murine small intestine after membrane permeabilization. We demonstrated that LP-PC-selective staining with PE-antibodies was not due to interactions of antibody-epitope or antibody-Fc receptor. This unexpected staining by PE-antibody was not dependent on the mouse strain of LP-PCs, experimental methods, or origin species of the antibody, but dependent on PE itself. This phenomenon was also observed in plasma cells isolated from bone marrow, spleen, and mesenteric lymph nodes. Furthermore, in vitro activated B cells and in vivo generated LP-PCs were also selectively stained by PE-conjugated antibodies. Taken together, these results show that PE-conjugated antibodies are inappropriate for intracellular staining of murine plasma cells.

  6. Albumin-Folate Conjugates for Drug-targeting in Photodynamic Therapy.

    Science.gov (United States)

    Butzbach, Kathrin; Rasse-Suriani, Federico A O; Gonzalez, M Micaela; Cabrerizo, Franco M; Epe, Bernd

    2016-07-01

    Photodynamic therapy (PDT) is based on the cytotoxicity of photosensitizers in the presence of light. Increased selectivity and effectivity of the treatment is expected if a specific uptake of the photosensitizers into the target cells, often tumor cells, can be achieved. An attractive transporter for that purpose is the folic acid receptor α (FRα), which is overexpressed on the surface of many tumor cells and mediates an endocytotic uptake. Here, we describe the synthesis and photobiological characterization of polar β-carboline derivatives as photosensitizers covalently linked to folate-tagged albumin as the carrier system. The particles were taken up by KB (human carcinoma) cells within albumin-β-carbolinium conjugate proved to be phototoxic, while the corresponding albumin-β-carbolinium conjugates without FA were nontoxic, both with and without irradiation. An excess of free folate as competitor for the FRα-mediated uptake completely inhibited the photocytotoxicity. Interestingly, the albumin conjugates are devoid of photodynamic activity under cell-free conditions, as shown for DNA as a target. Thus, phototoxicity requires cellular uptake and lysosomal degradation of the conjugates. In conclusion, albumin-folate conjugates appear to be promising vehicles for a tumor cell targeted PDT.

  7. Biological characterization of cetuximab-conjugated gold nanoparticles in a tumor animal model.

    Science.gov (United States)

    Kao, Hao-Wen; Lin, Yi-Yu; Chen, Chao-Cheng; Chi, Kwan-Hwa; Tien, Der-Chi; Hsia, Chien-Chung; Lin, Wuu-Jyh; Chen, Fu-Du; Lin, Ming-Hsien; Wang, Hsin-Ell

    2014-07-25

    Gold nanoparticles (AuNPs) are widely applied to the diagnosis and treatment of cancer and can be modified to contain target-specific ligands via gold-thiolate bonding. This study investigated the pharmacokinetics and microdistribution of antibody-mediated active targeting gold nanoparticles in mice with subcutaneous lung carcinoma. We conjugated AuNPs with cetuximab (C225), an antibody-targeting epidermal growth factor receptor (EGFR), and then labeled with In-111, which created EGFR-targeted AuNPs. In vitro studies showed that after a 2 h incubation, the uptake of C225-conjugated AuNPs in high EGFR-expression A549 cells was 14.9-fold higher than that of PEGylated AuNPs; furthermore, uptake was also higher at 3.8-fold when MCF7 cells with lower EGFR-expression were used. MicroSPECT/CT imaging and a biodistribution study conducted by using a A549 tumor xenograft mouse model provided evidence of elevated uptake of the C225-conjugated AuNPs into the tumor cells as a result of active targeting. Moreover, the microdistribution of PEGylated AuNPs revealed that a large portion of AuNPs remained in the tumor interstitium, whereas the C225-conjugated AuNPs displayed enhanced internalization via antibody-mediated endocytosis. Our findings suggest that the anti-EGFR antibody-conjugated AuNPs are likely to be a plausible nano-sized vehicle for drug delivery to EGFR-expressing tumors.

  8. Easy and Efficient 111Indium Labeling of Long-Term Stored DTPA Conjugated Protein

    DEFF Research Database (Denmark)

    Nalla, Amarnadh; Buch, Inge; Hesse, Birger

    2011-01-01

    targeting vehicles such as monoclonal antibodies and receptor directed peptides. The purpose of this study was to monitor the labelling efficiency of a DTPA-conjugate on long-term storage using 111In-chloride at two different temperatures and incubation times for the In-labelling. Method: Cyclic......-diethylene-triamine-pentaacetic acid (cDTAP) was conjugated to a polyclonal immunoglobulin-G (IgG) in borate buffer, pH 8.2 at +4?C for 4 hours. Then the DTPA-conjugate was dialyzed against 50 mmol/l sodium citrate buffer saline, pH 6.0 and stored at -80° C in aliquots of 1 mg/0.5 ml. The DTPA-conjugate was labeled with 111In...... months. Conclusion: Our study shows that 111In-labelling can easily be performed within 30 min at RT for thermo-stable proteins like polyclonal, DTPA-conjugated IgG stored long-term at -80°C with a high 111In-labelling efficiency....

  9. Easy and efficient (111)Indium labeling of long-term stored DTPA conjugated protein

    DEFF Research Database (Denmark)

    Nalla, Amarnadh; Buch, Inge; Hesse, Birger

    2011-01-01

    targeting vehicles such as monoclonal antibodies and receptor directed peptides. The purpose of this study was to monitor the labelling efficiency of a DTPA-conjugate on long-term storage using 111In-chloride at two different temperatures and incubation times for the In-labelling. Method: Cyclic......-diethylene-triamine-pentaacetic acid (cDTAP) was conjugated to a polyclonal immunoglobulin-G (IgG) in borate buffer, pH 8.2 at +4oC for 4 hours. Then the DTPA-conjugate was dialyzed against 50 mmol/l sodium citrate buffer saline, pH 6.0 and stored at -80o C in aliquots of 1 mg/0.5 ml. The DTPA-conjugate was labeled with 111In...... months. Conclusion: Our study shows that 111In-labelling can easily be performed within 30 min at RT for thermo-stable proteins like polyclonal, DTPA-conjugated IgG stored long-term at -80oC with a high 111In-labelling effi- ciency....

  10. Evaluation of iodovinyl antibody conjugates: Comparison with a p-iodobenzoyl conjugate and direct radioiodination

    Energy Technology Data Exchange (ETDEWEB)

    Hadley, S.W.; Wilbur, D.S. (NeoRx Corporation, Seattle, WA (USA))

    1990-03-01

    The preparations and conjugations of 2,3,5,6-tetrafluorophenyl 5-(125I/131I)iodo-4-pentenoate (7a) and 2,3,5,6-tetrafluorophenyl 3,3-dimethyl-5-(125I/131I)iodo-4-pentenoate (7b) to monoclonal antibodies are reported. Reagents 7a and 7b were prepared in high radiochemical yield by iododestannylation of their corresponding 5-tri-n-butylstannyl precursors. Radioiodinated antibody conjugates were prepared by reaction of 7a or 7b with the protein at basic pH. Evaluation of these conjugates by several in vitro procedures demonstrated that the radiolabel was attached to the antibody in a stable manner and that the conjugates maintained immunoreactivity. Comparative dual-isotope biodistribution studies of a monoclonal antibody Fab fragment conjugate of 7a and 7b with the same Fab fragment labeled with N-succinimidyl p-(131I)iodobenzoate (PIB, p-iodobenzoate, 2) or directly radioiodinated have been carried out in tumor-bearing nude mice. Coinjection of the Fab conjugate of 7a with the Fab conjugate of 2 demonstrated that the biodistributions were similar in most organs, except the neck tissue (thyroid-containing) and the stomach, which contained substantially increased levels of the 7a label. Coinjection of the Fab conjugate of 7a with the Fab fragment radioiodinated by using the chloramine-T method demonstrated that the biodistributions were remarkably similar, suggesting roughly equivalent in vivo deiodination of these labeled antibody fragments. Coinjection of the Fab conjugate of 7a with the Fab conjugate of 7b indicated that there was {approximately} a 2-fold reduction in the amount of in vivo deiodination of the 7b conjugate as compared to the 7a conjugate.

  11. Deciphering conjugative plasmid permissiveness in wastewater microbiomes

    DEFF Research Database (Denmark)

    Jacquiod, Samuel Jehan Auguste; Brejnrod, Asker Daniel; Milani, Stefan Morberg

    2017-01-01

    Wastewater treatment plants (WWTPs) are designed to robustly treat polluted water. They are characterized by ceaseless flows of organic, chemical and microbial matter, followed by treatment steps before environmental release. WWTPs are hotspots of horizontal gene transfer between bacteria via...... still remains largely uncharted. Furthermore, current in vitro methods used to assess conjugation in complex microbiomes do not include in situ behaviours of recipient cells, resulting in partial understanding of transfers. We investigated the in vitro conjugation capacities of WWTP microbiomes from...... diversity of recipient bacterial phyla for the plasmid was observed, especially in WWTP outlets. We also identified permissive bacteria potentially able to cross WWTPs and engage in conjugation before and after water treatment. Bacterial activity and lifestyle seem to influence conjugation extent...

  12. Conjugated amplifying polymers for optical sensing applications.

    Science.gov (United States)

    Rochat, Sébastien; Swager, Timothy M

    2013-06-12

    Thanks to their unique optical and electrochemical properties, conjugated polymers have attracted considerable attention over the last two decades and resulted in numerous technological innovations. In particular, their implementation in sensing schemes and devices was widely investigated and produced a multitude of sensory systems and transduction mechanisms. Conjugated polymers possess numerous attractive features that make them particularly suitable for a broad variety of sensing tasks. They display sensory signal amplification (compared to their small-molecule counterparts) and their structures can easily be tailored to adjust solubility, absorption/emission wavelengths, energy offsets for excited state electron transfer, and/or for use in solution or in the solid state. This versatility has made conjugated polymers a fluorescence sensory platform of choice in the recent years. In this review, we highlight a variety of conjugated polymer-based sensory mechanisms together with selected examples from the recent literature.

  13. Design and Application of Antimicrobial Peptide Conjugates

    Directory of Open Access Journals (Sweden)

    Andre Reinhardt

    2016-05-01

    Full Text Available Antimicrobial peptides (AMPs are an interesting class of antibiotics characterized by their unique antibiotic activity and lower propensity for developing resistance compared to common antibiotics. They belong to the class of membrane-active peptides and usually act selectively against bacteria, fungi and protozoans. AMPs, but also peptide conjugates containing AMPs, have come more and more into the focus of research during the last few years. Within this article, recent work on AMP conjugates is reviewed. Different aspects will be highlighted as a combination of AMPs with antibiotics or organometallic compounds aiming to increase antibacterial activity or target selectivity, conjugation with photosensitizers for improving photodynamic therapy (PDT or the attachment to particles, to name only a few. Owing to the enormous resonance of antimicrobial conjugates in the literature so far, this research topic seems to be very attractive to different scientific fields, like medicine, biology, biochemistry or chemistry.

  14. Hybrid electronics and electrochemistry with conjugated polymers.

    Science.gov (United States)

    Inganäs, Olle

    2010-07-01

    In this critical review, we discuss the history and development of polymer devices wherein manipulation of the electronic conductivity by electrochemical redox processes in a conjugated polymer is used to form new functions. The devices employed are an electrochemical transistor, an electrolyte-gated field-effect transistor and light-emitting electrochemical cells, all of which combine doping/undoping of a conjugated polymer with modification of electronic transport (130 references).

  15. Rapid modification of retroviruses using lipid conjugates

    Science.gov (United States)

    Mukherjee, Nimisha G.; Lyon, L. Andrew; LeDoux, Joseph M.

    2009-02-01

    Methods are needed to manipulate natural nanoparticles. Viruses are particularly interesting because they can act as therapeutic cellular delivery agents. Here we examine a new method for rapidly modifying retroviruses that uses lipid conjugates composed of a lipid anchor (1,2-distearoyl-sn-glycero-3-phosphoethanolamine), a polyethylene glycol chain, and biotin. The conjugates rapidly and stably modified retroviruses and enabled them to bind streptavidin. The implication of this work for modifying viruses for gene therapy and vaccination protocols is discussed.

  16. Energetic tuning in spirocyclic conjugated polymers

    OpenAIRE

    Hugo Bronstein; Frank D. King

    2016-01-01

    Precise control of the energy levels in a conjugated polymer is the key to allowing their exploitation in optoelectronic devices. The introduction of spirocycles into conjugated polymers has traditionally been used to enhance their solid state microstructure. Here we present a highly novel method of energetic tuning through the use of electronically active spirocyclic systems. By modifying the size and oxidation state of a heteroatom in an orthogonal spirocycle we demonstrate energetic fine t...

  17. Metal-leachate-induced conjugate protein instability.

    Science.gov (United States)

    Li, Ning; Osborne, Brandi; Singh, Satish K; Wang, Wei

    2012-08-01

    During the scale-up of an ultrafiltration/diafiltration (UF/DF) step for a protein-based conjugate vaccine, significant precipitation was observed at room temperature. It was found that a specific type of metal hosebarb fitting used in the UF/DF system, when placed in the conjugate solution, caused the precipitation. Inductively Coupled Plasma Mass Spectrometry analysis showed significant amounts of Ni(II), Zn(II), and Cu(II) present in the conjugate solution. A kinetic study showed that the concentration of these metal ions gradually increased with increasing incubation time with a corresponding decrease in conjugate concentration. Direct spiking of trace amounts of NiCl₂, ZnCl₂, and CuCl₂ into the conjugate solution also caused precipitation, and spiking studies showed that the metal ions caused precipitation of the conjugate but not of the carrier protein, antigen, or carrier protein + linker. The precipitation was found to be significantly dependent on buffer species but not solution pH and led to an irreversible loss of tertiary structure even after dissolution in and removal of guanidine hydrochloride. The precipitation is likely the result of formation of transition-metal complexes with histidine residues on the antigen peptide, which may involve both intraconjugate and interconjugate antigens. Such complexation may lead to formation of multimers that may exceed the solubility limit.

  18. Conjugated microporous polymers: design, synthesis and application.

    Science.gov (United States)

    Xu, Yanhong; Jin, Shangbin; Xu, Hong; Nagai, Atsushi; Jiang, Donglin

    2013-10-21

    Conjugated microporous polymers (CMPs) are a class of organic porous polymers that combine π-conjugated skeletons with permanent nanopores, in sharp contrast to other porous materials that are not π-conjugated and with conventional conjugated polymers that are nonporous. As an emerging material platform, CMPs offer a high flexibility for the molecular design of conjugated skeletons and nanopores. Various chemical reactions, building blocks and synthetic methods have been developed and a broad variety of CMPs with different structures and specific properties have been synthesized, driving the rapid growth of the field. CMPs are unique in that they allow the complementary utilization of π-conjugated skeletons and nanopores for functional exploration; they have shown great potential for challenging energy and environmental issues, as exemplified by their excellent performance in gas adsorption, heterogeneous catalysis, light emitting, light harvesting and electrical energy storage. This review describes the molecular design principles of CMPs, advancements in synthetic and structural studies and the frontiers of functional exploration and potential applications.

  19. Folic acid-CdTe quantum dot conjugates and their applications for cancer cell targeting

    Energy Technology Data Exchange (ETDEWEB)

    Suriamoorthy, Preethi; Zhang, Xing; Hao, Guiyang; Joly, Alan G.; Singh, S.; Hossu, Marius; Sun, Xiankai; Chen, Wei

    2010-12-01

    In this study, we report the preparation,luminescence, and targeting properties of folic acid- CdTe quantum dot conjugates. Water-soluble CdTe quantum dots were synthesized and conjugated with folic acid using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide-N-hydroxysuccinimide chemistry. The in-fluence of folic acid on the luminescence properties of CdTe quantum dots was investigated, and no energy transfer between them was observed. To investigate the efficiency of folic acid-CdTe nanoconjugates for tumor targeting, pure CdTe quantum dots and folic acid-coated CdTe quantum dots were incubated with human naso- pharyngeal epidermal carcinoma cell line with positive expressing folic acid receptors (KB cells) and lung cancer cells without expression of folic acid receptors (A549 cells). For the cancer cells with positive folate receptors (KB cells), the uptake for CdTe quantum dots is very low, but for folic acid-CdTe nanoconjugates, the uptake is very high. For the lung cancer cells without folate receptors (A549 cells), the uptake for folic acid- CdTe nanoconjugates is also very low. The results indicate that folic acid is an effective targeting molecule for tumor cells with overexpressed folate receptors.

  20. Easy and efficient (111)indium labeling of long-term stored DTPA conjugated protein.

    Science.gov (United States)

    Nalla, Amarnadh; Buch, Inge; Hesse, Birger

    2011-01-01

    The labelling efficiency of long-term stored DTPA-conjugates has not been reported previously even though DTPA has been in extensive use as metal chelator in the development of radiopharmaceuticals and contrast agents. DTPA is often used as a bifunctional chelating agent conjugated to tumor targeting vehicles such as monoclonal antibodies and receptor directed peptides. The purpose of this study was to monitor the labelling efficiency of a DTPA-conjugate on long-term storage using 111In-chloride at two different temperatures and incubation times for the In-labelling. Cyclic-diethylene-triamine-pentaacetic acid (cDTAP) was conjugated to a polyclonal immunoglobulin-G (IgG) in borate buffer, pH 8.2 at +4?C for 4 hours. Then the DTPA-conjugate was dialyzed against 50 mmol/l sodium citrate buffer saline, pH 6.0 and stored at -80° C in aliquots of 1 mg/0.5 ml. The DTPA-conjugate was labeled with 111In-chloride in citrate buffer, pH 6. The labelling reaction was incubated at room temperature (RT) for 30 min and at +4?C for 90 min. Determination of labelling efficiency was performed using ITLC and an instant chromatography scanner equipped with a NaI crystal. The labelling efficiency of the DTPA-conjugate was monitored every third month for 12 months. The median labelling efficiencies varied between 92 and 96% during the whole period. The two combinations of incubation times and temperatures (30 min at RT and 90 min at +4°C) had no affect on labelling efficiency of the DTPA-conjugate, stored for 12 months. Our study shows that 111In-labelling can easily be performed within 30 min at RT for thermo-stable proteins like polyclonal, DTPA-conjugated IgG stored long-term at -80°C with a high 111In-labelling efficiency.

  1. Geometric and Meshing Properties of Conjugate Curves for Gear Transmission

    Directory of Open Access Journals (Sweden)

    Dong Liang

    2014-01-01

    Full Text Available Conjugate curves have been put forward previously by authors for gear transmission. Compared with traditional conjugate surfaces, the conjugate curves have more flexibility and diversity in aspects of gear design and generation. To further extend its application in power transmission, the geometric and meshing properties of conjugate curves are discussed in this paper. Firstly, general principle descriptions of conjugate curves for arbitrary axial position are introduced. Secondly, geometric analysis of conjugate curves is carried out based on differential geometry including tangent and normal in arbitrary contact direction, characteristic point, and curvature relationships. Then, meshing properties of conjugate curves are further revealed. According to a given plane or spatial curve, the uniqueness of conjugated curve under different contact angle conditions is discussed. Meshing commonality of conjugate curves is also demonstrated in terms of a class of spiral curves contacting in the given direction for various gear axes. Finally, a conclusive summary of this study is given.

  2. PE-Cy5.5 conjugates bind to the cells expressing mouse DEC205/CD205

    Science.gov (United States)

    Park, Chae Gyu; Rodriguez, Anthony; Steinman, Ralph M.

    2012-01-01

    DEC205/CD205, an endocytic receptor of C-type multilectin, is expressed highly in dendritic cells (DCs). DEC205 was shown to efficiently deliver vaccine antigens in surrogate ligands to the antigen processing and presentation machinery of DCs, which resulted in the development of DC-targeted vaccines employing anti-DC monoclonal antibodies (mAbs). During our studies to characterize a variety of anti-DC mAbs including anti-DEC205 by flow cytometric analysis, we discovered that a secondary anti-immunoglobulin antibody conjugated with PE-Cy5.5 bound strongly to the cells expressing mouse DEC205 (mDEC205) without incubation of a primary anti-mDEC205 mAb. In the present study we demonstrate that various antibodies and streptavidin conjugated with PE-Cy5.5 bind to the mDEC205-expressing cells including CHO, KIT6, and HEK293 cells. The interaction between the PE-Cy5.5 conjugates and the cells expressing mDEC205 appears distinctive, since none of PE-Cy5.5 conjugates bind to the cells that express human DEC205 on surface. Besides, only PE-Cy5.5 conjugates bind strongly to mDEC205-expressing cells; PerCP-Cy5.5, APC-Cy5.5, and Cy5.5 conjugates bind weakly; PE, PE-Cy5, Cy5, FITC, or Alexa488 conjugates do not bind. Therefore the use of PE-Cy5.5 conjugates, widely utilized in multicolor flow cytometry, requires precaution against nonspecific binding to mDEC205-positive cells. PMID:22841832

  3. Outer membrane protein complex of Meningococcus enhances the antipolysaccharide antibody response to pneumococcal polysaccharide-CRM₁₉₇ conjugate vaccine.

    Science.gov (United States)

    Lai, Zengzu; Schreiber, John R

    2011-05-01

    Bacterial polysaccharides (PS) are T cell-independent antigens that do not induce immunologic memory and are poor immunogens in infants. Conjugate vaccines in which the PS is covalently linked to a carrier protein have enhanced immunogenicity that resembles that of T cell-dependent antigens. The Haemophilus influenzae type b (Hib) conjugate vaccine, which uses the outer membrane protein complex (OMPC) from meningococcus as a carrier protein, elicits protective levels of anti-capsular PS antibody (Ab) after a single dose, in contrast to other conjugate vaccines, which require multiple doses. We have previously shown that OMPC robustly engages Toll-like receptor 2 (TLR2) and enhances the early anti-Hib PS Ab titer associated with an increase in TLR2-mediated induction of cytokines. We now show that the addition of OMPC to the 7-valent pneumococcal PS-CRM₁₉₇ conjugate vaccine during immunization significantly increases the anti-PS IgG and IgM responses to most serotypes of pneumococcus contained in the vaccine. The addition of OMPC also increased the likelihood of anti-PS IgG3 production against serotypes 4, 6B, 9V, 18C, 19F, and 23F. Splenocytes from mice who had received OMPC with the pneumococcal conjugate vaccine produced significantly more interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ) than splenocytes from mice who received phosphate-buffered saline (PBS) plus the conjugate vaccine. We conclude that OMPC enhances the anti-PS Ab response to pneumococcal PS-CRM₁₉₇ conjugate vaccine, an effect associated with a distinct change in cytokine profile. It may be possible to reduce the number of conjugate vaccine doses required to achieve protective Ab levels by priming with adjuvants that are TLR2 ligands.

  4. Plant virus-resembling optical nano-materials conjugated with anti-EGFR for targeted cancer imaging

    Science.gov (United States)

    Gupta, Sharad; Wilder, Hailey; Rao, A. L. N.; Vullev, V. I.; Anvari, Bahman

    2012-03-01

    We recently reported the construction of a new type of optically active nano-particles composed of genome-depleted plant infecting brome mosaic virus (BMV) doped with indocyanine green (ICG), an FDA-approved chromophore . We refer to these constructs as optical viral ghosts (OVGs) since only the capsid protein (CP) subunits of BMV remain to encapsulate ICG. Herein, we covalently conjugated the surface of OVGs with anti-epidermal growth factor receptors (anti-EGFR) to target cancerous human bronchial epithelial cells (C-HBECs) in-vitro. Our preliminary results demonstrate the utility of conjugated OVGs for targeted imaging of cancer cells.

  5. Immunoglobulin and enzyme-conjugated dextran polymers enhance u-PAR staining intensity of carcinoma cells in peripheral blood smears

    DEFF Research Database (Denmark)

    Werther, K; Normark, M; Hansen, B F;

    1999-01-01

    phenotyping of disseminated carcinoma cells in bone marrow and peripheral blood smears. In the first step, the cells were incubated with antibodies against urokinase plasminogen activator receptor (u-PAR) and subsequently with secondary antibodies conjugated to peroxidase-labeled dextran polymers. A brown...... color reaction was developed with diaminobenzidine as chromogen. In the second step, the cells were incubated with alkaline phosphatase-conjugated murine monoclonal antibodies against a common cytokeratin epitope and a red color reaction was developed with new fuchsin as substrate. This method allows...

  6. Theoretical study of conjugated porphyrin polymers

    DEFF Research Database (Denmark)

    Pedersen, T.G.; Lynge, T.B.; Kristensen, P.K.

    2005-01-01

    The optical gap of conjugated triply linked porphyrin chains is exceptionally low (similar to 0.5 eV). Hence, such chains are candidates for organic infrared detectors and solar cells harvesting the infrared part of the solar spectrum. However, a low exciton binding energy is required for these a......The optical gap of conjugated triply linked porphyrin chains is exceptionally low (similar to 0.5 eV). Hence, such chains are candidates for organic infrared detectors and solar cells harvesting the infrared part of the solar spectrum. However, a low exciton binding energy is required...... for these applications. From a theoretical analysis of excitons in long metalloporphyrin chains, we demonstrate that the binding energy is much lower than in usual conjugated polymers. Our calculated absorption spectra are in good agreement with measurements. (c) 2004 Elsevier B.V. All rights reserved....

  7. Conjugate Meningococcal Vaccines Development: GSK Biologicals Experience

    Directory of Open Access Journals (Sweden)

    Jacqueline M. Miller

    2011-01-01

    Full Text Available Meningococcal diseases are serious threats to global health, and new vaccines specifically tailored to meet the age-related needs of various geographical areas are required. This paper focuses on the meningococcal conjugate vaccines developed by GSK Biologicals. Two combined conjugate vaccines were developed to help protect infants and young children in countries where the incidence of meningococcal serogroup C or serogroup C and Y disease is important: Hib-MenC-TT vaccine, which offers protection against Haemophilus influenzae type b and Neisseria meningitidis serogroup C diseases, is approved in several countries; and Hib-MenCY-TT vaccine, which adds N. meningitidis serogroup Y antigen, is currently in the final stages of development. Additionally, a tetravalent conjugate vaccine (MenACWY-TT designed to help protect against four meningococcal serogroups is presently being evaluated for global use in all age groups. All of these vaccines were shown to be highly immunogenic and to have clinically acceptable safety profiles.

  8. Chlorambucil gemcitabine conjugate nanomedicine for cancer therapy.

    Science.gov (United States)

    Fan, Mingliang; Liang, Xiaofei; Li, Zonghai; Wang, Hongyang; Yang, Danbo; Shi, Bizhi

    2015-11-15

    Self-assembly of anticancer small molecules into nanostructures may represent an attractive approach to improve the treatment of experimental solid tumors. As a proof of concept, we designed and synthesized the conjugate prodrug of hydrophilic gemcitabine by its covalent coupling to hydrophobic chlorambucil via a hydrolyzable ester linkage. The resulting amphiphilic conjugates self-assembled into nanoparticles in water and exhibited significant anticancer activity in vitro against a variety of human cancer cells. In vivo anticancer activity of these nanoparticles has been tested on subcutaneous grafted SMMC-7721 hepatocellular carcinoma model. Such chlorambucil gemcitabine conjugate nanomedicine should have potential applications in cancer therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. CO-releasing molecule (CORM) conjugate systems.

    Science.gov (United States)

    Kautz, Anna Christin; Kunz, Peter C; Janiak, Christoph

    2016-11-15

    The development of CORMs (CO-releasing molecules) as a prodrug for CO administration in living organisms has attracted significant attention. CORMs offer the promising possibility of a safe and controllable release of CO in low amounts triggered by light, ligands, enzymes, etc. For the targeting of specific tissues or diseases and to prevent possible side effects from metals and other residues after CO release, these CORMs are attached to biocompatible systems, like peptides, polymers, nanoparticles, dendrimers, protein cages, non-wovens, tablets, and metal-organic frameworks. We discuss in this review the known CORM carrier conjugates, in short CORM conjugates, with covalently-bound or incorporated CORMs for medicinal and therapeutic applications. Most conjugates are nontoxic, show increasing half-lives of CO release, and make use of the EPR-effect, but still show problems because of a continuous background of CO release and the absence of an on/off-switch for the CO release.

  10. Conjugate gradient algorithms using multiple recursions

    Energy Technology Data Exchange (ETDEWEB)

    Barth, T.; Manteuffel, T.

    1996-12-31

    Much is already known about when a conjugate gradient method can be implemented with short recursions for the direction vectors. The work done in 1984 by Faber and Manteuffel gave necessary and sufficient conditions on the iteration matrix A, in order for a conjugate gradient method to be implemented with a single recursion of a certain form. However, this form does not take into account all possible recursions. This became evident when Jagels and Reichel used an algorithm of Gragg for unitary matrices to demonstrate that the class of matrices for which a practical conjugate gradient algorithm exists can be extended to include unitary and shifted unitary matrices. The implementation uses short double recursions for the direction vectors. This motivates the study of multiple recursion algorithms.

  11. Tight-binding treatment of conjugated polymers

    DEFF Research Database (Denmark)

    Lynge, Thomas Bastholm

    This PhD thesis concerns conjugated polymers which constitute a constantly growing research area. Today, among other things, conjugated polymers play a role in plastic based solar cells, photodetectors and light emitting diodes, and even today such plastic-based components constitute an alternative...... of tomorrow. This thesis specifically treats the three conjugated polymers trans-polyacetylene (tPA), poly(para-phenylene) (PPP) and poly(para-phe\\-nylene vinylene) (PPV). The present results, which are derived within the tight-binding model, are divided into two parts. In one part, analytic results...... are derived for the optical properties of the polymers expressed in terms of the optical susceptibility both in the presence and in the absence of a static electric field. In the other part, the cumputationally efficient Density Functional-based Tight-Binding (DFTB) model is applied to the description...

  12. Novel β-cyclodextrin–eosin conjugates

    Directory of Open Access Journals (Sweden)

    Gábor Benkovics

    2017-03-01

    Full Text Available Eosin B (EoB and eosin Y (EoY, two xanthene dye derivatives with photosensitizing ability were prepared in high purity through an improved synthetic route. The dyes were grafted to a 6-monoamino-β-cyclodextrin scaffold under mild reaction conditions through a stable amide linkage using the coupling agent 4-(4,6-dimethoxy-1,3,5-triazin-2-yl-4-methylmorpholinium chloride. The molecular conjugates, well soluble in aqueous medium, were extensively characterized by 1D and 2D NMR spectroscopy and mass spectrometry. Preliminary spectroscopic investigations showed that the β-cyclodextrin–EoY conjugate retains both the fluorescence properties and the capability to photogenerate singlet oxygen of the unbound chromophore. In contrast, the corresponding β-cyclodextrin–EoB conjugate did not show either relevant emission or photosensitizing activity probably due to aggregation in aqueous medium, which precludes any response to light excitation.

  13. Folate-conjugated gold nanoparticle as a new nanoplatform for targeted cancer therapy.

    Science.gov (United States)

    Samadian, Hadi; Hosseini-Nami, Samira; Kamrava, Seyed Kamran; Ghaznavi, Habib; Shakeri-Zadeh, Ali

    2016-11-01

    Conventional cancer treatment methods suffer from many limitations such as non-specificity and low efficacy in discrimination between healthy and cancer cells. Recent developments in nanotechnology have introduced novel and smart therapeutic nanomaterials that basically take advantage of various targeting approaches. Targeted nanomaterials selectively bind to the cancer cells and affect them with minor effects on healthy cells. Folic acid (folate) is an essential molecule in DNA synthesis pathway which is highly needed for cancer cell duplication. Some certain cancer cells overexpress folate receptors higher than normal cells, and this fact is the basis of folate targeting strategy. There are many publications reporting various folate conjugated nanomaterials among which folate-conjugated gold nanoparticles hold great promises in targeted cancer therapy. Gold nanoparticles have been identified as promising candidates for new cancer therapy modalities because of biocompatibility, easy synthesis and functionalization, chemo-physical stability, and optical tunable characteristics. In the last decade, there has been a significant explosion in gold nanoparticles research, with a rapid increase in publications related to the area of biomedicine. Although there are many reports published on "gold nanoparticles" and "folate targeting," there are a few reports on "folate-conjugated gold nanoparticles" in biomedical literature. This paper intends to review and illustrate the recent advances in biomedicine which have been designed on the basis of folate-conjugated gold nanoparticles.

  14. Quantification and imaging of HER2 protein using nanocrystals conjugated with single-domain antibodies

    Science.gov (United States)

    Glukhov, S.; Berestovoy, M.; Chames, P.; Baty, D.; Nabiev, I.; Sukhanova, A.

    2017-01-01

    This study dealt with quantification and imaging of human epidermal growth factor receptor 2 (HER2), an important prognostic marker for cancer diagnosis and treatment, using specific quantum-dot-based conjugates. Fluorescent inorganic nanocrystals or quantum dots (QDs) are extremely highly resistant to photobleaching and have a high emission quantum yield and a continuous range of emission spectra, from the ultraviolet to the infrared regions. Ultrasmall nanoprobes consisting of highly affine anti-HER2 single-domain antibodies (sdAbs or "nanobodies") conjugated with QDs in a strictly oriented manner have been designed. QDs with a fluorescence peak maxima at wavelengths of 562 nm, 569 nm, 570 nm or in the near-infrared region were used. Here, we present our results of ISA quantification of HER2 protein, in situ imaging of HER2 protein on the surface of HER2-positive SK-BR-3 cells in immunohistochemical experiments, and counting of stained with anti-HER2 conjugates HER2-positive SK-BR-3 cells in their mixture with unstained cells of the same culture in flow cytometry experiments. The data demonstrate that the anti-HER2 QD-sdAb conjugates obtained are highly specific and sensitive and could be used in numerous applications for advanced integrated diagnosis.

  15. Comparative Analysis of Nanoparticle-Antibody Conjugations: Carbodiimide Versus Click Chemistry

    Directory of Open Access Journals (Sweden)

    Daniel L.J. Thorek

    2009-07-01

    Full Text Available The ability to modify the physical, chemical, and biologic properties of nanoparticles has led to their use as multifunctional platforms for drug delivery and diagnostic imaging applications. Typically, these applications involve functionalizing the nanoparticles with targeting agents. Antibodies remain an attractive choice as targeting agents because of their large epitope space and high affinity; however, implementation of antibody-nanoparticle conjugates is plagued by low coupling efficiencies and the high cost of reagents. Click chemistry may provide a solution to this problem, with reported coupling efficiencies nearing 100%. Although click chemistries have been used to functionalize nanoparticles with small molecules, they have not previously been used to functionalize nanoparticles with antibodies. Concerns associated with extending this procedure to antibodies are that reaction catalysts or the ligands required for cross-linking may result in loss of functionality. We evaluated the efficiency of conjugations between antibodies and superparamagnetic iron oxide nanoparticles using click chemistry as well as the functionality of the product. The results were compared with conjugates formed through carbodiimide cross-linking. The click reaction allowed for a higher extent and efficiency of labeling compared with carbodiimide, thus requiring less antibody. Further, conjugates prepared via the click reaction exhibited improved binding to target receptors.

  16. Phase conjugation of high energy lasers.

    Energy Technology Data Exchange (ETDEWEB)

    Bliss, David E; Valley, Michael T.; Atherton, Briggs W.; Bigman, Verle Howard; Boye, Lydia Ann; Broyles, Robin Scott; Kimmel, Mark W.; Law, Ryan J.; Yoder, James R.

    2013-01-01

    In this report we explore claims that phase conjugation of high energy lasers by stimulated Brillouin scattering (SBS) can compensate optical aberrations associated with severely distorted laser amplifier media and aberrations induced by the atmosphere. The SBS media tested was a gas cell pressurized up to 300 psi with SF6 or Xe or both. The laser was a 10 Hz, 3J, Q-switched Nd:YAG with 25 ns wide pulses. Atmospheric aberrations were created with space heaters, helium jets and phase plates designed with a Kolmogorov turbulence spectrum characterized by a Fried parameter, ro , ranging from 0.6 6.0 mm. Phase conjugate tests in the laboratory were conducted without amplification. For the strongest aberrations, D/ro ~ 20, created by combining the space heaters with the phase plate, the Strehl ratio was degraded by a factor of ~50. Phase conjugation in SF6 restored the peak focusable intensity to about 30% of the original laser. Phase conjugate tests at the outdoor laser range were conducted with laser amplifiers providing gain in combination with the SBS cell. A large 600,000 BTU kerosene space heater was used to create turbulence along the beam path. An atmospheric structure factor of Cn2 = 5x10-13 m2/3 caused the illumination beam to expand to a diameter 250mm and overfill the receiver. The phase conjugate amplified return could successfully be targeted back onto glints 5mm in diameter. Use of a lenslet arrays to lower the peak focusable intensity in the SBS cell failed to produce a useful phase conjugate beam; The Strehl ratio was degraded with multiple random lobes instead of a single focus. I will review literature results which show how multiple beams can be coherently combined by SBS when a confocal reflecting geometry is used to focus the laser in the SBS cell.

  17. METHOD OF CONJUGATED CIRCULAR ARCS TRACING

    Directory of Open Access Journals (Sweden)

    N. Ageyev Vladimir

    2017-01-01

    Full Text Available The geometric properties of conjugated circular arcs connecting two points on the plane with set directions of tan- gent vectors are studied in the work. It is shown that pairs of conjugated circular arcs with the same conditions in frontier points create one-parameter set of smooth curves tightly filling all the plane. One of the basic properties of this set is the fact that all coupling points of circular arcs are on the circular curve going through the initially given points. The circle radius depends on the direction of tangent vectors. Any point of the circle curve, named auxiliary in this work, determines a pair of conjugated arcs with given boundary conditions. One more condition of the auxiliary circle curve is that it divides the plane into two parts. The arcs going from the initial point are out of the circle limited by this circle curve and the arcs coming to the final point are inside it. These properties are the basis for the method of conjugated circular arcs tracing pro- posed in this article. The algorithm is rather simple and allows to fulfill all the needed plottings using only the divider and ruler. Two concrete examples are considered. The first one is related to the problem of tracing of a pair of conjugated arcs with the minimal curve jump when going through the coupling point. The second one demonstrates the possibility of trac- ing of the smooth curve going through any three points on the plane under condition that in the initial and final points the directions of tangent vectors are given. The proposed methods of conjugated circular arcs tracing can be applied in solving of a wide variety of problems connected with the tracing of cam contours, for example pattern curves in textile industry or in computer-aided-design systems when programming of looms with numeric control.

  18. Synthesis of cyanopyridine based conjugated polymer

    Directory of Open Access Journals (Sweden)

    B. Hemavathi

    2016-06-01

    Full Text Available This data file contains the detailed synthetic procedure for the synthesis of two new cyanopyridine based conjugated polymer P1 and P2 along with the synthesis of its monomers. The synthesised polymers can be used for electroluminescence and photovoltaic (PV application. The physical data of the polymers are provided in this data file along with the morphological data of the polymer thin films. The data provided here are in association with the research article entitled ‘Cyanopyridine based conjugated polymer-synthesis and characterisation’ (Hemavathi et al., 2015 [3].

  19. Conjugate metamaterials and the perfect lens

    CERN Document Server

    Xu, Yadong; Xu, Lin; Chen, Huanyang

    2015-01-01

    In this letter, we show how transformation optics makes it possible to design what we call conjugate metamaterials. We show that these materials can also serve as substrates for making a subwavelength-resolution lens. The so-called "perfect lens", which is a lens that could focus all components of light (including propagating and evanescent waves), can be regarded as a limiting case, in which the respective conjugate metamaterials approach the characteristics of left-handed metamaterials, which have a negative refractive index.

  20. Conjugated Polymers as Actuators: Modes of Actuation

    DEFF Research Database (Denmark)

    Skaarup, Steen

    The physical and chemical properties of conjugated polymers often depend very strongly on the degree of doping with anions or cations. The movement of ions in and out of the polymer matrix as it is redox cycled is also accompanied by mechanical changes. Both the volume and the stiffness can exhibit...... significant differences between the oxidized and reduced states. These effects form the basis of the use of conjugated polymers as actuators (or “artificial muscles”) controllable by a small (1-10 V) voltage. Three basic modes of actuation (bending, linear extension and stiffness change) have been proposed...

  1. Conjugated polymers as actuators: modes of actuation

    DEFF Research Database (Denmark)

    Skaarup, Steen

    2007-01-01

    The physical and chemical properties of conjugated polymers often depend very strongly on the degree of doping with anions or cations. The movement of ions in and out of the polymer matrix as it is redox cycled is also accompanied by mechanical changes. Both the volume and the stiffness can exhibit...... significant differences between the oxidized and reduced states. These effects form the basis of the use of conjugated polymers as actuators (or “artificial muscles”) controllable by a small (1-10 V) voltage. Three basic modes of actuation (bending, linear extension and stiffness change) have been proposed...

  2. [Conjugate vaccines against bacterial infections: typhoid fever].

    Science.gov (United States)

    Paniagua, J; García, J A; López, C R; González, C R; Isibasi, A; Kumate, J

    1992-01-01

    Capsular polysaccharides have been studied as possible vaccines against infectious diseases. However, they are capable to induce only short-run protection because of their T-independent properties and they would not be protective against infection in high-risk populations. The alternative to face this problem is to develop methods to join covalently the polysaccharide and proteins to both increase the immunogenicity of and to confer the property of T-dependence to this antigen. In order to obtain a conjugate vaccine against typhoid fever, in our laboratory we have tried to synthesize a conjugate immunogen between the Vi antigen and porins from Salmonella typhi.

  3. Dynamics of Photogenerated Polarons in Conjugated Polymers

    Science.gov (United States)

    An, Z.; Wu, C. Q.; Sun, X.

    2004-11-01

    Within a tight-binding electron-phonon interacting model, we investigate the dynamics of photoexcitations to address the generation mechanism of charged polarons in conjugated polymers by using a nonadiabatic evolution method. Besides the neutral polaron exciton which is well known, we identify a novel product of lattice dynamic relaxation from the photoexcited states in a few hundreds of femtoseconds, which is a mixed state composed of both charged polarons and neutral excitons. Our results show that the charged polarons are generated directly with a yield of about 25%, which is independent of the excitation energies, in good agreement with results from experiments. Effects of the conjugation length are also discussed.

  4. Functionalized conjugated polyelectrolytes design and biomedical applications

    CERN Document Server

    Wang, Shu

    2014-01-01

    Functionalized Conjugated Polyelectrolytes presents a comprehensive review of these polyelectrolytes and their biomedical applications. Basic aspects like molecular design and optoelectronic properties are covered in the first chapter. Emphasis is placed on the various applications including sensing (chemical and biological), disease diagnosis, cell imaging, drug/gene delivery and disease treatment. This book explores a multi-disciplinary topic of interest to researchers working in the fields of chemistry, materials, biology and medicine. It also offers an integrated perspective on both basic research and application issues. Functionalized conjugated polyelectrolyte materials, which have already drawn considerable interest, will become a major new direction for biomedicine development.

  5. Intracellular delivery and trafficking dynamics of a lymphoma-targeting antibody-polymer conjugate.

    Science.gov (United States)

    Berguig, Geoffrey Y; Convertine, Anthony J; Shi, Julie; Palanca-Wessels, Maria Corinna; Duvall, Craig L; Pun, Suzie H; Press, Oliver W; Stayton, Patrick S

    2012-12-03

    Ratiometric fluorescence and cellular fractionation studies were employed to characterize the intracellular trafficking dynamics of antibody-poly(propylacrylic acid) (PPAA) conjugates in CD22+ RAMOS-AW cells. The HD39 monoclonal antibody (mAb) directs CD22-dependent, receptor-mediated uptake in human B-cell lymphoma cells, where it is rapidly trafficked to the lysosomal compartment. To characterize the intracellular-release dynamics of the polymer-mAb conjugates, HD39-streptavidin (HD39/SA) was dual-labeled with pH-insensitive Alexa Fluor 488 and pH-sensitive pHrodo fluorophores. The subcellular pH distribution of the HD39/SA-polymer conjugates was quantified as a function of time by live-cell fluorescence microscopy, and the average intracellular pH value experienced by the conjugates was also characterized as a function of time by flow cytometry. PPAA was shown to alter the intracellular trafficking kinetics strongly relative to HD39/SA alone or HD39/SA conjugates with a control polymer, poly(methacryclic acid) (PMAA). Subcellular trafficking studies revealed that after 6 h, only 11% of the HD39/SA-PPAA conjugates had been trafficked to acidic lysosomal compartments with values at or below pH 5.6. In contrast, the average intracellular pH of HD39/SA alone dropped from 6.7 ± 0.2 at 1 h to 5.6 ± 0.5 after 3 h and 4.7 ± 0.6 after 6 h. Conjugation of the control polymer PMAA to HD39/SA showed an average pH drop similar to that of HD39/SA. Subcellular fractionation studies with tritium-labeled HD39/SA demonstrated that after 6 h, 89% of HD39/SA was associated with endosomes (Rab5+) and lysosomes (Lamp2+), while 45% of HD39/SA-PPAA was translocated to the cytosol (lactate dehydrogenase+). These results demonstrate the endosomal-releasing properties of PPAA with antibody-polymer conjugates and detail their intracellular trafficking dynamics and subcellular compartmental distributions over time.

  6. Multiplexed detection of various breast cancer cells by perfluorocarbon/quantum dot nanoemulsions conjugated with antibodies

    Science.gov (United States)

    Bae, Pan Kee; Chung, Bong Hyun

    2014-07-01

    The effective targeting of cancer cell surface antigens is an attractive approach in cancer diagnosis and therapy. Multifunctional nanoprobes with cell-targeting specificity are likely to find important applications in bioanalysis, biomedicine, and clinical diagnosis. In this study, we have fabricated biocompatible perfluorocan/quantum dot nanoemulsions as bimodal imaging nanoprobes for the targeting of breast cancer cells. Perfluorocarbon/quantum dot nanoemulsions conjugated with monoclonal antibodies, as a type of bimodal imaging nanoprobe based on 19 F-MR and optical imaging, have been synthesized and applied for targeted imaging of three different breast cancer cells (SKBR3, MCF-7, MDA-MB 468), respectively. We have shown that the cancer-detection capabilities of antibody-conjugated PFC/QDs nanoemulsions could be successfully applied to target of various breast cancer cells. These modified PFC/QDs nanoemulsions were shown to target the cancer cell surface receptors specially. Conjugation of ligands to nanoemulsions targeting over-expressed cell surface receptors is a promising approach for targeted imaging to tumor cells. We further propose that the PFC/QDs nanoemulsions could be used in targeted imaging of breast cancer cells.

  7. Conjugate Gradient Methods with Armijo-type Line Searches

    Institute of Scientific and Technical Information of China (English)

    Yu-Hong DAI

    2002-01-01

    Two Armijo-type line searches are proposed in this paper for nonlinear conjugate gradient methods.Under these line searches, global convergence results are established for several famous conjugate gradient method.

  8. Meningococcal conjugate vaccines: optimizing global impact

    Directory of Open Access Journals (Sweden)

    Terranella A

    2011-09-01

    Full Text Available Andrew Terranella1,2, Amanda Cohn2, Thomas Clark2 1Epidemic Intelligence Service, Division of Applied Sciences, Scientific Education and Professional Development Program Office, 2Meningitis and Vaccine Preventable Diseases Branch, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA Abstract: Meningococcal conjugate vaccines have several advantages over polysaccharide vaccines, including the ability to induce greater antibody persistence, avidity, immunologic memory, and herd immunity. Since 1999, meningococcal conjugate vaccine programs have been established across the globe. Many of these vaccination programs have resulted in significant decline in meningococcal disease in several countries. Recent introduction of serogroup A conjugate vaccine in Africa offers the potential to eliminate meningococcal disease as a public health problem in Africa. However, the duration of immune response and the development of widespread herd immunity in the population remain important questions for meningococcal vaccine programs. Because of the unique epidemiology of meningococcal disease around the world, the optimal vaccination strategy for long-term disease prevention will vary by country. Keywords: conjugate vaccine, meningitis, meningococcal vaccine, meningococcal disease

  9. Conjugate Problems in Convective Heat Transfer: Review

    Directory of Open Access Journals (Sweden)

    Abram Dorfman

    2009-01-01

    Full Text Available A review of conjugate convective heat transfer problems solved during the early and current time of development of this modern approach is presented. The discussion is based on analytical solutions of selected typical relatively simple conjugate problems including steady-state and transient processes, thermal material treatment, and heat and mass transfer in drying. This brief survey is accompanied by the list of almost two hundred publications considering application of different more and less complex analytical and numerical conjugate models for simulating technology processes and industrial devices from aerospace systems to food production. The references are combined in the groups of works studying similar problems so that each of the groups corresponds to one of selected analytical solutions considered in detail. Such structure of review gives the reader the understanding of early and current situation in conjugate convective heat transfer modeling and makes possible to use the information presented as an introduction to this area on the one hand, and to find more complicated publications of interest on the other hand.

  10. Women experiencing the intergenerationality of conjugal violence

    Directory of Open Access Journals (Sweden)

    Gilvânia Patrícia do Nascimento Paixão

    2015-10-01

    Full Text Available Objective: to analyze the family relationship, in childhood and adolescence, of women who experience conjugal violence.Method: qualitative study. Interviews were held with 19 women, who were experiencing conjugal violence, and who were resident in a community in Salvador, Bahia, Brazil. The project was approved by the Research Ethics Committee (N. 42/2011.Results: the data was organized using the Discourse of the Collective Subject, identifying the summary central ideas: they witnessed violence between their parents; they suffered repercussions from the violence between their parents: they were angry about the mother's submission to her partner; and they reproduced the conjugal violence. The discourse showed that the women witnessed, in childhood and adolescence, violence between their parents, and were injured both physically and psychologically. As a result of the mother's submission, feelings of anger arose in the children. However, in the adult phase of their own lives, they noticed that their conjugal life resembled that of their parents, reproducing the violence.Conclusion: investment is necessary in strategies designed to break inter-generational violence, and the health professionals are important in this process, as it is a phenomenon with repercussions in health. Because they work in the Family Health Strategy, which focuses on the prevention of harm and illness, health promotion and interdepartmentality, the nurses are essential in the process of preventing and confronting this phenomenon.

  11. Antibody-drug conjugates: Intellectual property considerations.

    Science.gov (United States)

    Storz, Ulrich

    2015-01-01

    Antibody-drug conjugates are highly complex entities that combine an antibody, a linker and a toxin. This complexity makes them demanding both technically and from a regulatory point of view, and difficult to deal with in their patent aspects. This article discusses different issues of patent protection and freedom to operate with regard to this promising new class of drugs.

  12. Transparency in Bragg scattering and phase conjugation.

    Science.gov (United States)

    Longhi, S

    2010-11-15

    Reflectionless transmission of light waves with unitary transmittance is shown to occur in a certain class of gain-grating structures and phase-conjugation mirrors in the unstable (above-threshold) regime. Such structures are synthesized by means of the Darboux method developed in the context of supersymmetric relativistic quantum mechanics. Transparency is associated to superluminal pulse transmission.

  13. Compositions for directed alignment of conjugated polymers

    Science.gov (United States)

    Kim, Jinsang; Kim, Bong-Gi; Jeong, Eun Jeong

    2016-04-19

    Conjugated polymers (CPs) achieve directed alignment along an applied flow field and a dichroic ratio of as high as 16.67 in emission from well-aligned thin films and fully realized anisotropic optoelectronic properties of CPs in field-effect transistor (FET).

  14. Some aspects of geomagnetically conjugate phenomena

    Energy Technology Data Exchange (ETDEWEB)

    Rycroft, M.J.

    1987-12-01

    Both charged particles and waves convey information about the thermosphere, ionosphere and magnetosphere from the Northern to the Southern Hemisphere and vice versa, along geomagnetic flux tubes.The interhemispheric travel time of electrons or ions, being dependent upon L-value , pitch angle and energy (which may lie between less than or equal to 1 eV and greater than or equal to 1 MeV) may be many hours, ranging down to less than or equal to 1 s. However, the one-hop propagation time for magnetohydrodynamic or whistler mode waves generally lies between 10/sup 2/s and 1 s. Such times, therefore, give the time scales of transient phenomena that are geomagnetically conjugate and of changes in steady-state plasma processes occurring in geomagnetically conjugate regions. Contrasting examples are presented of conjugate physical phenomena, obtained using satellite, rocket, aircraft and ground-based observations; the latter capitalise upon the rather rare disposition of land - rather than ocean - at each end of a geophysically interesting flux tube. Particular attention is paid to the interactions between whistler mode waves and energetic electrons. Geomagnetic, radio, optical and plasma observations, taken together with model computations, provide a wealth of knowledge on conjugate phenomena and their dependence on conditions in the solar wind, substorms, L-value, etc... Finally, some suggestions are made for future lines of research.

  15. Conjugation-uniqueness of exact Borel subalgebras

    Institute of Scientific and Technical Information of China (English)

    张跃辉

    1999-01-01

    It is proved that the exact Borel subalgebras of a basic quasi-hereditary algebra are conjugate to each other. Moreover, the inner automorphism group of a basic quasi-hereditary algebra acts transitively on the set of its exact Borel subalgebras.

  16. Predicting the optical gap of conjugated systems

    Science.gov (United States)

    Botelho, Andre Leitao

    The adapted Su-Schrieffer-Heeger model is developed in this work as a tool for in silico prediction of the optical gap of pi-conjugated systems for photovoltaic applications. Full transferability of the model ensures reliable predictive power - excellent agreement with 180 independent experimental data points covering virtually all existing conjugated system types with an accuracy exceeding the time-dependent density functional theory, one of the most accurate first-principles methods. Insights on the structure-property relation of conjugated systems obtained from the model lead to guiding rules for optical gap design: 1) fusing aromatic rings parallel to the conjugated path does not significantly lower the optical gap, 2) fusing rings perpendicularly lowers the optical gap of the monomer, but has a reduced benefit from polymerization, and 3) copolymers take advantage of the lower optical gap of perpendicular fused rings and benefit from further optical gap reduction through added parallel fused rings as electronic communicators. A copolymer of parallel and perpendicular benzodithiophenes, differing only in sulfur atom locations, is proposed as a candidate to achieve the optimal 1.2 eV donor optical gap for organic photovoltaics. For small-molecule organic photovoltaics, substituting the end pairs of carbon atoms on pentacene with sulfur atoms is predicted to lower the optical gap from 1.8 eV to 1.1 eV. Furthermore, the model offers an improvement of orders of magnitude in the computational efficiency over commonly used first-principles tools.

  17. Photorefractive phase-conjugation digital holographic microscopy

    Science.gov (United States)

    Chang, Chi-Ching; Chan, Huang-Tian; Shiu, Min-Tzung; Chew, Yang-Kun

    2015-05-01

    In this work, we propose an innovative method for digital holographic microscopy named as photorefractive phaseconjugation digital holographic microscopy (PPCDHM) technique based on the phase conjugation dynamic holographic process in photorefractive BaTiO3 crystal and the retrieval of phase and amplitude of the object wave were performed by a reflection-type digital holographic method. Both amplitude and phase reconstruction benefit from the prior amplification by self-pumped conjugation (SPPC) as they have an increased SNR. The interest of the PPCDHM is great, because its hologram is created by interfered the amplified phase-conjugate wave field generated from a photorefractive phase conjugator (PPC) correcting the phase aberration of the imaging system and the reference wave onto the digital CCD camera. Therefore, a precise three-dimensional description of the object with high SNR can be obtained digitally with only one hologram acquisition. The method requires the acquisition of a single hologram from which the phase distribution can be obtained simultaneously with distribution of intensity at the surface of the object.

  18. Conjugate problems in convective heat transfer

    CERN Document Server

    Dorfman, Abram S

    2009-01-01

    The conjugate heat transfer (CHT) problem takes into account the thermal interaction between a body and fluid flowing over or through it, a key consideration in both mechanical and aerospace engineering. Presenting more than 100 solutions of non-isothermal and CHT problems, this title considers the approximate solutions of CHT problems.

  19. Conjugal Succession and the American Kinship System.

    Science.gov (United States)

    Furstenberg, Frank F., Jr.

    Although not the preferred type of family formation, conjugal succession is now an accepted, if not expected, alternative to continuous marriage in the United States. This new trend appears to be related to a shift in the meaning of matrimony. Previously, marriage was part of a cultural pattern of transitions and as such was closely timed to…

  20. Metal coordination of ferrocene-histidine conjugates.

    Science.gov (United States)

    Ferranco, Annaleizle; Basak, Shibaji; Lough, Alan; Kraatz, Heinz-Bernhard

    2017-04-05

    This study presents a few bis(histidine) ligands working to build a small peptidic model system of zinc structural sites. Ferrocene-peptide conjugates Fc[CO-His(Trt)-His(Trt)-OMe]2 (3), Fc[CO-His(Trt)-Asp(OMe)-OMe]2 (4), and Fc[CO-His(Trt)-Glu(OMe)-OMe]2 (5) were synthesized and characterized spectroscopically. (1)H-NMR and IR spectroscopic studies reveal hydrogen bonding interactions and while more detailed circular dichroism studies show a 1,2'-P helical "Herrick conformation" for Fc-conjugates 4 and 5, we discovered M-helical chirality in Fc-peptide 3. The half-wave potentials (E1/2) of ferrocene-peptides follow the sequence 3 anodic potential shifts upon the addition of metal ions, which follow the order Cu(2+) > Zn(2+) > Ni(2+) > Cd(2+) > Mn(2+) > Mg(2+). NMR spectroscopic experiments show that the two nitrogen atoms present on each imidazole ring of His residues are the site of metal coordination. There is a strong indication that peptide conjugates 4 and 5 in the presence of Zn(2+) enforce a coordination number of four as the CD spectra of Fc-conjugates 4 and 5 exhibited a red shift which corresponds to the third and fourth coordination sites occupied by neutral carbonyl oxygen donor atoms, in addition, carbonyl amide appears downward shifted in wavenumber upon metal addition.

  1. Continuous flow synthesis of conjugated polymers.

    Science.gov (United States)

    Seyler, Helga; Jones, David J; Holmes, Andrew B; Wong, Wallace W H

    2012-02-01

    A selection of conjugated polymers, widely studied in organic electronics, was synthesised using continuous flow methodology. As a result of superior heat transfer and reagent control, excellent polymer molecular mass distributions were achieved in significantly reduced reaction times compared to conventional batch reactions.

  2. Vibrational Spectroscopy of Microhydrated Conjugate Base Anions

    NARCIS (Netherlands)

    Asmis, K. R.; Neumark, D. M.

    2012-01-01

    Conjugate-base anions are ubiquitous in aqueous solution. Understanding the hydration of these anions at the molecular level represents a long-standing goal in chemistry. A molecular-level perspective on ion hydration is also important for understanding the surface speciation and reactivity of aeros

  3. Bacillus thuringiensis Conjugation in Simulated Microgravity

    Science.gov (United States)

    Beuls, Elise; van Houdt, Rob; Leys, Natalie; Dijkstra, Camelia; Larkin, Oliver; Mahillon, Jacques

    2009-10-01

    Spaceflight experiments have suggested a possible effect of microgravity on the plasmid transfer among strains of the Gram-positive Bacillus thuringiensis, as opposed to no effect recorded for Gram-negative conjugation. To investigate these potential effects in a more affordable experimental setup, three ground-based microgravity simulators were tested: the Rotating Wall Vessel (RWV), the Random Positioning Machine (RPM), and a superconducting magnet. The bacterial conjugative system consisted in biparental matings between two B. thuringiensis strains, where the transfer frequencies of the conjugative plasmid pAW63 and its ability to mobilize the nonconjugative plasmid pUB110 were assessed. Specifically, potential plasmid transfers in a 0-g position (simulated microgravity) were compared to those obtained under 1-g (normal gravity) condition in each device. Statistical analyses revealed no significant difference in the conjugative and mobilizable transfer frequencies between the three different simulated microgravitational conditions and our standard laboratory condition. These important ground-based observations emphasize the fact that, though no stimulation of plasmid transfer was observed, no inhibition was observed either. In the case of Gram-positive bacteria, this ability to exchange plasmids in weightlessness, as occurs under Earth's conditions, should be seen as particularly relevant in the scope of spread of antibiotic resistances and bacterial virulence.

  4. Stochastic differential equations used to model conjugation

    DEFF Research Database (Denmark)

    Philipsen, Kirsten Riber; Christiansen, Lasse Engbo

    Stochastic differential equations (SDEs) are used to model horizontal transfer of antibiotic resis- tance by conjugation. The model describes the concentration of donor, recipient, transconjugants and substrate. The strength of the SDE model over the traditional ODE models is that the noise can...

  5. Theory of periodic conjugate heat transfer

    CERN Document Server

    Zudin, Yuri B

    2016-01-01

    This book presents the theory of periodic conjugate heat transfer in detail. It offers a simplified description of the interaction between a solid body and a fluid as a boundary value problem of the heat conduction equation for the solid body.

  6. Electromagnetic wave propagations in conjugate metamaterials.

    Science.gov (United States)

    Xu, Yadong; Fu, Yangyang; Chen, Huanyang

    2017-03-06

    In this work, by employing field transformation optics, we deduce a special kind of materials called conjugate metamaterials, which can support intriguing electromagnetic wave propagations, such as negative refractions and lasing phenomena. These materials could also serve as substrates for making a subwavelength-resolution lens, and the so-called "perfect lens" is demonstrated to be a limiting case.

  7. Synthesis of Indomethacin Conjugates with D-Glucosamine

    Institute of Scientific and Technical Information of China (English)

    Yi Chun ZHANG; Ying Xia LI; Hua Shi GUAN

    2005-01-01

    Two series of indomethacin conjugates with D-glucosamine were prepared with the objectives of reducing ulcerogenic potency, increasing the bioavailability of indomethacin and exerting the coordinative effects on osteoarthritis. The structures of the conjugates were identified by 1H NMR and 13C NMR. The ester conjugates inhibited edema as potent as indomethacin.

  8. Cross-Conjugated n-Dopable Aromatic Polyketone

    NARCIS (Netherlands)

    Voortman, Thomas P.; Bartesaghi, Davide; Koster, L. Jan Anton; Chiechi, Ryan C.

    2015-01-01

    This paper describes the synthesis and characterization of a high molecular weight cross-conjugated polyketone synthesized via scalable Friedel Crafts chemistry. Cross-conjugated polyketones are precursors to conjugated polyions; they become orders of magnitude more conductive after a two-electron r

  9. Conjugated Educational System: Notion, Structure, Educational Potential 

    OpenAIRE

    Andrei A. Ostapenko; Dar'ya S. Tkach

    2012-01-01

    The article indicates the ways to decrease risk from teenagers and youth’s growing-up in today’s Russia by development of fundamental models of conjugated educational systems and their mass implementation in educational practice, introduces the notion of “conjugated educational system” for scientific use, describes types of conjugation and educational results of submitted models use.

  10. Cross-Conjugated n-Dopable Aromatic Polyketone

    NARCIS (Netherlands)

    Voortman, Thomas P.; Bartesaghi, Davide; Koster, L. Jan Anton; Chiechi, Ryan C.

    2015-01-01

    This paper describes the synthesis and characterization of a high molecular weight cross-conjugated polyketone synthesized via scalable Friedel Crafts chemistry. Cross-conjugated polyketones are precursors to conjugated polyions; they become orders of magnitude more conductive after a two-electron

  11. The adjuvant effect of TLR7 agonist conjugated to a meningococcal serogroup C glycoconjugate vaccine.

    Science.gov (United States)

    Donadei, Agnese; Balocchi, Cristiana; Mancini, Francesca; Proietti, Daniela; Gallorini, Simona; O'Hagan, Derek T; D'Oro, Ugo; Berti, Francesco; Baudner, Barbara C; Adamo, Roberto

    2016-10-01

    Conjugation of a small molecule immunopotentiator to antigens has been proposed to deliver the ligand to the receptor, localize its action and minimize systemic inflammation. However, the effect of conjugation of Toll like receptor 7 agonists (TLR7a) on the immunogenicity of carbohydrate-based vaccines is unknown. In this study we synthesized an anti-Neisseria meningitidis serogroup C (MenC) glycoconjugate vaccine composed of MenC oligosaccharide antigens covalently linked to the carrier protein CRM197, to which a TLR7a was in turn conjugated. This vaccine was able to activate in vitro the TLR7 comparably to the unconjugated ligand. The magnitude and the quality of the immune response against MenC capsular polysaccharide were evaluated in mice, comparing the MenC-CRM-TLR7a construct to a MenC-CRM197 vaccine, prepared through the same conjugation chemistry and co-administered with the unconjugated TLR7a. A commercially licensed anti-MenC glycoconjugate was used as further control to determine the influence of the coupling approach and the level of carbohydrate incorporation on the anti-MenC immune response. The possible additive effect of co-administration with Alum hydroxide (AlumOH) was also examined. The bactericidal titers against N. meningitidis were in agreement with the elicited anti-carbohydrate IgGs, and unequivocally showed that TLR7a conjugation to CRM197 enhanced the anti-MenC immune response. TLR7a conjugation induced a shift to a Th1 type response, as assessed by the increased IgG2a subclass production, both in the absence and in the presence of AlumOH. The increased immune response was clearly present only in the absence of AlumOH and was less pronounced than the co-administration of a licensed glycoconjugate with a standard dose of TLR7a-phosphonate adsorbed on the inorganic salt. The amount of MenC saccharide that was covalently linked to CRM197 after previous CRM197-TLR7a conjugation resulted in lower responses than achieved with conventional Men

  12. Endogenous Bioactive Jasmonate Is Composed of a Set of (+)-7-iso-JA-Amino Acid Conjugates.

    Science.gov (United States)

    Yan, Jianbin; Li, Suhua; Gu, Min; Yao, Ruifeng; Li, Yuwen; Chen, Juan; Yang, Mai; Tong, Jianhua; Xiao, Langtao; Nan, Fajun; Xie, Daoxin

    2016-12-01

    Jasmonates (JAs) regulate a wide range of plant defense and development processes. The bioactive JA is perceived by its receptor COI1 to trigger the degradation of JASMONATE ZIM-DOMAIN (JAZ) proteins and subsequently derepress the JAZ-repressed transcription factors for activation of expression of JA-responsive genes. So far, (+)-7-iso-JA-l-Ile has been the only identified endogenous bioactive JA molecule. Here, we designed coronafacic acid (CFA) conjugates with all the amino acids (CFA-AA) to mimic the JA amino acid conjugates, and revealed that (+)-7-iso-JA-Leu, (+)-7-iso-JA-Val, (+)-7-iso-JA-Met, and (+)-7-iso-JA-Ala are new endogenous bioactive JA molecules. Furthermore, our studies uncover the general characteristics for all the bioactive JA molecules, and provide a new strategy to synthetically generate novel active JA molecules.

  13. Targeting of follicle stimulating hormone peptide-conjugated dendrimers to ovarian cancer cells

    Science.gov (United States)

    Modi, Dimple A.; Sunoqrot, Suhair; Bugno, Jason; Lantvit, Daniel D.; Hong, Seungpyo; Burdette, Joanna E.

    2014-02-01

    Ovarian cancer is the most lethal gynecological malignancy. Current treatment modalities include a combination of surgery and chemotherapy, which often lead to loss of fertility in premenopausal women and a myriad of systemic side effects. To address these issues, we have designed poly(amidoamine) (PAMAM) dendrimers to selectively target the follicle stimulating hormone receptor (FSHR), which is overexpressed by tumorigenic ovarian cancer cells but not by immature primordial follicles and other non-tumorigenic cells. Fluorescein-labeled generation 5 (G5) PAMAM dendrimers were conjugated with the binding peptide domain of FSH (FSH33) that has a high affinity to FSHR. The targeted dendrimers exhibited high receptor selectivity to FSHR-expressing OVCAR-3 cells, resulting in significant uptake and downregulation of an anti-apoptotic protein survivin, while showing minimal interactions with SKOV-3 cells that do not express FSHR. The selectivity of the FSH33-targeted dendrimers was further validated in 3D organ cultures of normal mouse ovaries. Immunostaining of the conjugates revealed their selective binding and uptake by ovarian surface epithelium (OSE) cells that express FSHR, while sparing the immature primordial follicles. In addition, an in vivo study monitoring tissue accumulation following a single intraperitoneal (i.p.) injection of the conjugates showed significantly higher accumulation of FSH33-targeted dendrimers in the ovary and oviduct compared to the non-targeted conjugates. These proof-of-concept findings highlight the potential of these FSH33-targeted dendrimers to serve as a delivery platform for anti-ovarian cancer drugs, while reducing their systemic side effects by preventing nonspecific uptake by the primordial follicles.Ovarian cancer is the most lethal gynecological malignancy. Current treatment modalities include a combination of surgery and chemotherapy, which often lead to loss of fertility in premenopausal women and a myriad of systemic side

  14. Conjugating folate on superparamagnetic Fe3O4@Au nanoparticles using click chemistry

    Science.gov (United States)

    Shen, Xiaofang; Ge, Zhaoqiang; Pang, Yuehong

    2015-02-01

    Gold-coated magnetic core@shell nanoparticles, which exhibit magneto-optical properties, not only enhance the chemical stability of core and biocompatibility of surface, but also provide a combination of multimodal imaging and therapeutics. The conjugation of these tiny nanoparticles with specific biomolecules allows researchers to target the desired location. In this paper, superparamagnetic Fe3O4@Au nanoparticles were synthesized and functionalized with the azide group on the surface by formation of self-assembled monolayers. Folate (FA) molecules, non-immunogenic target ligands for cancer cells, are conjugated with alkyne and then immobilized on the azide-terminated Fe3O4@Au nanoparticles through copper(I)-catalyzed azide-alkyne cycloaddition (click reaction). Myelogenous leukemia K562 cells were used as a folate receptor (FR) model, which can be targeted and extracted by magnetic field after interaction with the Fe3O4@Au-FA nanoparticles.

  15. Resolution of Digitized Conjugate Tooth-Face Surface Based on the Theory of Digitized Conjugate Surfaces

    Institute of Scientific and Technical Information of China (English)

    XIAO Lai-yuan; LIAO Dao-xun; YI Chuan-yun

    2004-01-01

    According to the principle of meshing engagement and the theory of the digitized conjugate surface, this paper applies the software Conjugater-l. 0 that is developed by ourselves to compute, respectivcly, the digitized conjugate curved surfaces of the straight-tooth surface and drum-tooth surface,which will establish the theoretical and technical foundation for digitized engaging analysis, simulation, and digitized manufacturing technology of the diversified gears.

  16. Elucidation of the Biotransformation Pathways of a Galnac3-conjugated Antisense Oligonucleotide in Rats and Monkeys

    Directory of Open Access Journals (Sweden)

    Colby S Shemesh

    2016-01-01

    Full Text Available Triantennary N-acetyl galactosamine (GalNAc3 is a high-affinity ligand for hepatocyte-specific asialoglycoprotein receptors. Conjugation with GalNAc3 via a trishexylamino (THA-C6 cluster significantly enhances antisense oligonucleotide (ASO potency. Herein, the biotransformation, disposition, and elimination of the THA cluster of ION-681257, a GalNAc3-conjugated ASO currently in clinical development, are investigated in rats and monkey. Rats were administered a single subcutaneous dose of 3H-radiolabeled (3H placed in THA or nonradiolabeled ION-681257. Mass balance included radiometric profiling and metabolite fractionation with characterization by mass spectrometry. GalNAc3-conjugated ASOs were extensively distributed into liver. The THA-C6 triantenerrary GalNAc3 conjugate at the 5′-end of the ASO was rapidly metabolized and excreted with 25.67 ± 1.635% and 71.66 ± 4.17% of radioactivity recovered in urine and feces within 48 hours postdose. Unchanged drug, short-mer ASOs, and linker metabolites were detected in urine. Collectively, 14 novel linker associated metabolites were discovered including oxidation at each branching arm, initially by monooxidation at the β-position followed by dioxidation at the α-arm, and lastly, tri and tetra oxidations on the two remaining β-arms. Metabolites in bile and feces were identical to urine except for oxidized linear and cyclic linker metabolites. Enzymatic reaction phenotyping confirmed involvement of N-acetyl-β-glucosaminidase, deoxyribonuclease II, alkaline phosphatase, and alcohol + aldehyde dehydrogenases on the complex metabolism pathway for THA supplementing in vivo findings. Lastly, excreta from monkeys treated with ION-681257 revealed the identical series as observed in rat. In summary, our findings provide an improved understanding of GalNAc3-conjugated-ASO metabolism pathways which facilitate similar development programs.

  17. Comparison of three different conjugation strategies in the construction of herceptin-bearing paclitaxel-loaded nanoparticles.

    Science.gov (United States)

    Yu, Kongtong; Zhou, Yulin; Li, Yuhuan; Sun, Xiangshi; Sun, Fengying; Wang, Xinmei; Mu, Hongyan; Li, Jie; Liu, Xiaoyue; Teng, Lesheng; Li, Youxin

    2016-08-19

    Research on quantitatively controlling the ligand density on the surface of nanocarriers is in the frontier and becomes a technical difficulty for targeted delivery system designing. In this study, we developed an improved pre-conjugation (Imp) strategy, in which herceptin as a ligand was pre-conjugated with DSPE-PEG2000-Mal via chemical cross-linking, followed by conjugation onto the surface of pre-prepared paclitaxel-loaded PLGA/DODMA nanoparticles (PDNs) through hydrophobic interaction and electrostatic attraction for paclitaxel delivery. Compared with the post-conjugation (Pos) strategy, in which the ligand was conjugated onto the nanoparticle surface after the preparation of the nanoparticles, it realized a precise control targeting effect via adjustment of the herceptin density on the surface of the nanoparticles. Within the range of 0-20% of DSPE-PEG2000-herceptin in the blend, it showed a linear relation with the ligand density on the surface of the nanoparticles. The Imp strategy protected the bioactivity of the ligand during the preparation of nanoparticles. At the same time it avoided the waste of an excess amount of herceptin to drive the conjugation reaction in comparison with the post-conjugation (Pos) strategy. The nanoparticles from the Imp strategy showed much better cytotoxicity (p < 0.001), tumor targeting and cellular uptake efficiency (p < 0.001) than that of the other strategies in BT474 cells, in which BT474 cells were HER2 receptor over-expression breast cancer cell lines. A significant reduction in cellular uptake of the nanoparticles from the Imp strategy was observed in the presence of sucrose and cytochalasin D, indicating that clathrin-mediated and caveolae-dependent endocytosis was as a primary mechanism of cellular entry for these antibody-modified nanoparticles.

  18. Rational design, biophysical and biological characterization of site-specific antibody-tubulysin conjugates with improved stability, efficacy and pharmacokinetics.

    Science.gov (United States)

    Thompson, Pamela; Fleming, Ryan; Bezabeh, Binyam; Huang, Fengying; Mao, Shenlan; Chen, Cui; Harper, Jay; Zhong, Haihong; Gao, Xizhe; Yu, Xiang-Qing; Hinrichs, Mary Jane; Reed, Molly; Kamal, Adeela; Strout, Patrick; Cho, Song; Woods, Rob; Hollingsworth, Robert E; Dixit, Rakesh; Wu, Herren; Gao, Changshou; Dimasi, Nazzareno

    2016-08-28

    Antibody-drug conjugates (ADCs) are among the most promising empowered biologics for cancer treatment. ADCs are commonly prepared by chemical conjugation of small molecule cytotoxic anti-cancer drugs to antibodies through either lysine side chains or cysteine thiols generated by the reduction of interchain disulfide bonds. Both methods yield heterogeneous conjugates with complex biophysical properties and suboptimal serum stability, efficacy, and pharmacokinetics. To limit the complexity of cysteine-based ADCs, we have engineered and characterized in vitro and in vivo antibody cysteine variants that allow precise control of both site of conjugation and drug load per antibody molecule. We demonstrate that the chemically-defined cysteine-engineered antibody-tubulysin conjugates have improved ex vivo and in vivo stability, efficacy, and pharmacokinetics when compared to conventional cysteine-based ADCs with similar drug-to-antibody ratios. In addition, to limit the non-target FcγRs mediated uptake of the ADCs by cells of the innate immune system, which may result in off-target toxicities, the ADCs have been engineered to lack Fc-receptor binding. The strategies described herein are broadly applicable to any full-length IgG or Fc-based ADC and have been incorporated into an ADC that is in phase I clinical development.

  19. The biosynthesis of N-arachidonoyl dopamine (NADA), a putative endocannabinoid and endovanilloid, via conjugation of arachidonic acid with dopamine.

    Science.gov (United States)

    Hu, Sherry Shu-Jung; Bradshaw, Heather B; Benton, Valery M; Chen, Jay Shih-Chieh; Huang, Susan M; Minassi, Alberto; Bisogno, Tiziana; Masuda, Kim; Tan, Bo; Roskoski, Robert; Cravatt, Benjamin F; Di Marzo, Vincenzo; Walker, J Michael

    2009-10-01

    N-arachidonoyl dopamine (NADA) is an endogenous ligand that activates the cannabinoid type 1 receptor and the transient receptor potential vanilloid type 1 channel. Two potential biosynthetic pathways for NADA have been proposed, though no conclusive evidence exists for either. The first is the direct conjugation of arachidonic acid with dopamine and the other is via metabolism of a putative N-arachidonoyl tyrosine (NA-tyrosine). In the present study we investigated these biosynthetic mechanisms and report that NADA synthesis requires TH in dopaminergic terminals; however, NA-tyrosine, which we identify here as an endogenous lipid, is not an intermediate. We show that NADA biosynthesis primarily occurs through an enzyme-mediated conjugation of arachidonic acid with dopamine. While this conjugation likely involves a complex of enzymes, our data suggest a direct involvement of fatty acid amide hydrolase in NADA biosynthesis either as a rate-limiting enzyme that liberates arachidonic acid from AEA, or as a conjugation enzyme, or both.

  20. Visualization of phase conjugate ultrasound waves passed through inhomogeneous layer.

    Science.gov (United States)

    Yamamoto, K; Pernod, P; Preobrazhensky, V

    2004-04-01

    Compensation of phase distortions of ultrasound beams by means of parametric phase conjugation is visualized. Quasi-plane and focused primary beams were distorted by a polymer aberration layer introduced between the primary wave source and the wave phase conjugator. It is demonstrated acousto-optically that, while the acoustic field is strongly irregular in the area between aberration layer and conjugator, the phase conjugate wave visibly reproduces the primary beams in the area between the layer and the primary wave source. The phenomenon is observed in supercritical mode of parametric amplification when intensity of phase conjugate wave is high enough for manifestations of acoustic nonlinearities in water.

  1. Conjugation of mono and di-GalNAc sugars enhances the potency of antisense oligonucleotides via ASGR mediated delivery to hepatocytes.

    Science.gov (United States)

    Kinberger, Garth A; Prakash, Thazha P; Yu, Jinghua; Vasquez, Guillermo; Low, Audrey; Chappell, Alfred; Schmidt, Karsten; Murray, Heather M; Gaus, Hans; Swayze, Eric E; Seth, Punit P

    2016-08-01

    Antisense oligonucleotides (ASOs) conjugated to trivalent GalNAc ligands show 10-fold enhanced potency for suppressing gene targets expressed in hepatocytes. Trivalent GalNAc is a high affinity ligand for the asialoglycoprotein receptor (ASGR)-a C-type lectin expressed almost exclusively on hepatocytes in the liver. In this communication, we show that conjugation of two and even one GalNAc sugar to single stranded chemically modified ASOs can enhance potency 5-10 fold in mice. Evaluation of the mono- and di-GalNAc ASO conjugates in an ASGR binding assay suggested that chemical features of the ASO enhance binding to the receptor and provide a rationale for the enhanced potency.

  2. PRINCIPLE AND TRANSMISSION TECHNOLOGY OF BERTRAND CONJUGATE SURFACES

    Institute of Scientific and Technical Information of China (English)

    DUAN Zhenyun; CHEN Houjun; LIU Jian

    2006-01-01

    Bertrand surface is presented by abstracting and subliming the common characteristic of the usual surfaces including rotational surfaces, developable surfaces, normal circular-arc surfaces,etc. Basic characteristic of Bertrand surface is that normals along generator are coplanar. Bertrand conjugate principle is studied and its basic characteristic is that the instantaneous contact line between a pair of Bertrand conjugate surfaces is generator. Bertrand conjugate can be divided into three kinds of typical conjugation forms in terms of the generators that are general plane curve, circular-arc and straight line. Basic conjugate condition is given respectively, and structure condition, which reflects transmission forms and directrix characteristic of this kind of conjugation, is researched. As typical engineering application of Bertrand conjugate surface principle, transmission technology of loxodromic-type normal circular-arc bevel gear is studied.

  3. Highly sensitive biosensors based on water-soluble conjugated polymers

    Institute of Scientific and Technical Information of China (English)

    XU Hui; WU Haiping; FAN Chunhai; LI Wenxin; ZHANG Zhizhou; HE Lin

    2004-01-01

    Conjugated, conductive polymers are a kind of important organic macromolecules, which has found applications in a variety of areas. The application of conjugated polymers in developing fluorescent biosensors represents the merge of polymer sciences and biological sciences. Conjugated polymers are very good light harvesters as well as fluorescent polymers, and they are also "molecular wires". Through elaborate designs, these important features, i.e. efficient light harvesting and electron/energy transfer, can be used as signal amplification in fluorescent biosensors. This might significantly improve the sensitivity of conjugated polymer-based biosensors. In this article, we reviewed the application of conjugated polymers, via either electron transfer or energy transfer, to detections of gene targets, antibodies or enzymes. We also reviewed recent efforts in conjugated polymer-based solid-state sensor designs as well as chip-based multiple target detection. Possible directions in this conjugated polymer-based biosensor area are also discussed.

  4. Folic Acid-Chitosan Conjugated Nanoparticles for Improving Tumor-Targeted Drug Delivery

    Directory of Open Access Journals (Sweden)

    Huijuan Song

    2013-01-01

    Full Text Available Objective. To prepare folic acid-chitosan conjugated nanoparticles (FA-CS NPs and evaluate their targeting specificity on tumor cells. Methods. Chitosan (CS NPs were prepared by ionic cross linking method, and folic acid (FA was conjugated with CS NPs by electrostatic interaction. The properties of NPs were investigated, and doxorubicin hydrochloride (Dox as a model drug was encapsulated for investigating drug release pattern in vitro. The cytotoxicity and cellular uptake of FA-CS NPs were also investigated. Results. The results reveal that the obtained FA-CS NPs were monodisperse nanoparticles with suitable average size and positive surface charge. Dox was easily loaded into FA-CS NPs, and the release pattern showed a long and biphasic drug release. Noticeable phagocytosis effect was observed in the presence of rhodamine B-labeled FA-CSNPs when incubating with the folate receptor-positive SMMC-7221 cells. Conclusion. Compared with the unmodified CS NPs, FA-CS NPs showed much higher cell uptaking ability due to the known folate-receptor mediated endocytosis. FA-CS NPs provide a potential way to enhance the using efficiency of antitumor drug by folate receptor mediated targeting delivery.

  5. Anti-Lymphoma Efficacy Comparison of Anti-Cd20 Monoclonal Antibody-Targeted and Non-Targeted Star-Shaped Polymer-Prodrug Conjugates

    Directory of Open Access Journals (Sweden)

    Ondřej Lidický

    2015-11-01

    Full Text Available Here we describe the synthesis and biological properties of two types of star-shaped polymer-doxorubicin conjugates: non-targeted conjugate prepared as long-circulating high-molecular-weight (HMW polymer prodrugs with a dendrimer core and a targeted conjugate with the anti-CD20 monoclonal antibody (mAb rituximab (RTX. The copolymers were linked to the dendrimer core or to the reduced mAb via one-point attachment forming a star-shaped structure with a central antibody or dendrimer surrounded by hydrophilic polymer chains. The anticancer drug doxorubicin (DOX was attached to the N-(2-hydroxypropylmethacrylamide (HPMA-based copolymer chain in star polymer systems via a pH-labile hydrazone linkage. Such polymer-DOX conjugates were fairly stable in aqueous solutions at pH 7.4, and the drug was readily released in mildly acidic environments at pH 5–5.5 by hydrolysis of the hydrazone bonds. The cytotoxicity of the polymer conjugates was tested on several CD20-positive or negative human cell lines. Similar levels of in vitro cytotoxicity were observed for all tested polymer conjugates regardless of type or structure. In vivo experiments using primary cell-based murine xenograft models of human diffuse large B-cell lymphoma confirmed the superior anti-lymphoma efficacy of the polymer-bound DOX conjugate when compared with the original drug. Targeting with RTX did not further enhance the anti-lymphoma efficacy relative to the non-targeted star polymer conjugate. Two mechanisms could play roles in these findings: changes in the binding ability to the CD-20 receptor and a significant loss of the immunological properties of RTX in the polymer conjugates.

  6. Quorum Sensing N-acyl Homoserine Lactones-SdiA Suppresses Escherichia coli-Pseudomonas aeruginosa Conjugation through Inhibiting traI Expression

    Science.gov (United States)

    Lu, Yang; Zeng, Jianming; Wu, Binning; E, Shunmei; Wang, Lina; Cai, Renxin; Zhang, Ni; Li, Youqiang; Huang, Xianzhang; Huang, Bin; Chen, Cha

    2017-01-01

    Conjugation is a key mechanism for horizontal gene transfer and plays an important role in bacterial evolution, especially with respect to antibiotic resistance. However, little is known about the role of donor and recipient cells in regulation of conjugation. Here, using an Escherichia coli (SM10λπ)-Pseudomonas aeruginosa (PAO1) conjugation model, we demonstrated that deficiency of lasI/rhlI, genes associated with generation of the quorum sensing signals N-acyl homoserine lactones (AHLs) in PAO1, or deletion of the AHLs receptor SdiA in the donor SM10λπ both facilitated conjugation. When using another AHLs-non-producing E. coli strain EC600 as recipient cells, deficiency of sdiA in donor SM10λπ hardly affect the conjugation. More importantly, in the presence of exogenous AHLs, the conjugation efficiency between SM10λπ and EC600 was dramatically decreased, while deficiency of sdiA in SM10λπ attenuated AHLs-inhibited conjugation. These data suggest the conjugation suppression function of AHLs-SdiA chemical signaling. Further bioinformatics analysis, β-galactosidase reporter system and electrophoretic mobility shift assays characterized the binding site of SdiA on the promoter region of traI gene. Furthermore, deletion of lasI/rhlI or sdiA promoted traI mRNA expression in SM10λπ and PAO1 co-culture system, which was abrogated by AHLs. Collectively, our results provide new insight into an important contribution of quorum sensing system AHLs-SdiA to the networks that regulate conjugation. PMID:28164039

  7. A new daunomycin-peptide conjugate: synthesis, characterization and the effect on the protein expression profile of HL-60 cells in vitro.

    Science.gov (United States)

    Orbán, Erika; Manea, Marilena; Marquadt, Andreas; Bánóczi, Zoltán; Csík, Gabriella; Fellinger, Erzsébet; Bosze, Szilvia; Hudecz, Ferenc

    2011-10-19

    Daunomycin (Dau) is a DNA-binding antineoplastic agent in the treatment of various types of cancer, such as osteosarcomas and acute myeloid leukemia. One approach to improve its selectivity and to decrease the side effects is the conjugation of Dau with oligopeptide carriers, which might alter the drug uptake and intracellular fate. Here, we report on the synthesis, characterization, and in vitro biological properties of a novel conjugate in which Dau is attached, via an oxime bond, to one of the cancer specific small peptides (LTVSPWY) selected from a random phage peptide library. The in vitro cytostatic effect and cellular uptake of Dau═Aoa-LTVSPWY-NH(2) conjugate were studied on various human cancer cell lines expressing different levels of ErbB2 receptor which could be targeted by the peptide. We found that the new daunomycin-peptide conjugate is highly cytostatic and could be taken up efficiently by the human cancer cells studied. However, the conjugate was less effective than the free drug itself. RP-HPLC data indicate that the conjugate is stable at least for 24 h in the pH 2.5-7.0 range of buffers, as well as in cell culture medium. The conjugate in the presence of rat liver lysosomal homogenate, as indicated by LC-MS analysis, could be degraded. The smallest, Dau-containing metabolite (Dau═Aoa-Leu-OH) identified and prepared expresses DNA-binding ability. In order to get insight on the potential mechanism of action, we compared the protein expression profile of HL-60 human leukemia cells after treatment with the free and peptide conjugated daunomycin. Proteomic analysis suggests that the expression of several proteins has been altered. This includes three proteins, whose expression was lower (tubulin β chain) or markedly higher (proliferating cell nuclear antigen and protein kinase C inhibitor protein 1) after administration of cells with Dau-conjugate vs free drug.

  8. Conjugation of fluorescent proteins with DNA oligonucleotides.

    Science.gov (United States)

    Lapiene, Vidmantas; Kukolka, Florian; Kiko, Kathrin; Arndt, Andreas; Niemeyer, Christof M

    2010-05-19

    This work describes the synthesis of covalent ssDNA conjugates of six fluorescent proteins, ECFP, EGFP, E(2)GFP, mDsRed, Dronpa, and mCherry, which were cloned with an accessible C-terminal cystein residue to enable site-selective coupling using a heterobispecific cross-linker. The resulting conjugates revealed similar fluorescence emission intensity to the unconjugated proteins, and the functionality of the tethered oligonucleotide was proven by specific Watson-Crick base pairing to cDNA-modified gold nanoparticles. Fluorescence spectroscopy analysis indicated that the fluorescence of the FP is quenched by the gold particle, and the extent of quenching varied with the intrinsic spectroscopic properties of FP as well as with the configuration of surface attachment. Since this study demonstrates that biological fluorophores can be selectively incorporated into and optically coupled with nanoparticle-based devices, applications in DNA-based nanofabrication can be foreseen.

  9. Health benefits of conjugated linoleic acid (CLA).

    Science.gov (United States)

    Koba, Kazunori; Yanagita, Teruyoshi

    2014-01-01

    Conjugated linoleic acid (CLA) is a group of positional and geometric (cis or trans) isomers of linoleic acid with a conjugated double bond. The most representative CLA isomers are 9c,11t-18:2 and 10t,12c-18:2. CLA has been shown to exert various potent physiological functions such as anticarcinogenic, antiobese, antidiabetic and antihypertensive properties. This means CLA can be effective to prevent lifestyle diseases or metabolic syndromes. Also, reports suggest that physiological effects of CLA are different between the isomers, for example the 10t,12c isomer is anticarcinogenic, antiobese and antidiabetic, whereas the 9c,11t isomer is mainly anticarcinogenic. We describe here the physiological properties of CLA including the possible mechanism and the possibility to benefit human health.

  10. Discrete modelling of bacterial conjugation dynamics

    CERN Document Server

    Goni-Moreno, Angel

    2012-01-01

    In bacterial populations, cells are able to cooperate in order to yield complex collective functionalities. Interest in population-level cellular behaviour is increasing, due to both our expanding knowledge of the underlying biological principles, and the growing range of possible applications for engineered microbial consortia. Researchers in the field of synthetic biology - the application of engineering principles to living systems - have, for example, recently shown how useful decision-making circuits may be distributed across a bacterial population. The ability of cells to interact through small signalling molecules (a mechanism known as it quorum sensing) is the basis for the majority of existing engineered systems. However, horizontal gene transfer (or conjugation) offers the possibility of cells exchanging messages (using DNA) that are much more information-rich. The potential of engineering this conjugation mechanism to suit specific goals will guide future developments in this area. Motivated by a l...

  11. Solventless processing of conjugated polymers - a review

    OpenAIRE

    Brandão, Lúcia; Viana, Júlio; Bucknall, David G.; Bernardo, Gabriel

    2014-01-01

    The molecular mobility of polymers in their solid or molten states allows their processing without the need for toxic, “non-friendly” solvents. In this work, the main features of solvent-free processing methods applied to conjugated polymers are reviewed taking into consideration that these materials are largely used in a broad range of (opto-)electronic applications, including organic field-effect transistors, polymer light-emitting diodes and polymer photovoltaic devices. This review addres...

  12. Solventless processing of conjugated polymers - a review

    OpenAIRE

    Brandão, Lúcia; Viana, Júlio; Bucknall, David G.; Bernardo, Gabriel

    2014-01-01

    The molecular mobility of polymers in their solid or molten states allows their processing without the need for toxic, “non-friendly” solvents. In this work, the main features of solvent-free processing methods applied to conjugated polymers are reviewed taking into consideration that these materials are largely used in a broad range of (opto-)electronic applications, including organic field-effect transistors, polymer light-emitting diodes and polymer photovoltaic devices. This review addres...

  13. Conjugated Polymer Actuators: Prospects and Limitations

    DEFF Research Database (Denmark)

    Skaarup, Steen

    2007-01-01

    Actuators constructed with a conjugated polymer as the active part have been predicted to have a number of highly desirable properties: Large mechanical strength, high power density, i.e. high actuation speeds possible, sufficient maximum strain values, high reversibility and safe, low voltages (1......-5 V), . Taking status after about 15 years of research efforts, most of these predictions have come true, the main exception being the much lower speeds actually realized in actuators....

  14. Conjugated Linoleic Acid: good or bad nutrient

    Directory of Open Access Journals (Sweden)

    Gonçalves Daniela C

    2010-10-01

    Full Text Available Abstract Conjugated linoleic acid (CLA is a class of 28 positional and geometric isomers of linoleic acid octadecadienoic.Currently, it has been described many benefits related to the supplementation of CLA in animals and humans, as in the treatment of cancer, oxidative stress, in atherosclerosis, in bone formation and composition in obesity, in diabetes and the immune system. However, our results show that, CLA appears to be not a good supplement in patients with cachexia.

  15. Applications of Conjugated Polymers to DNA Sensing

    Institute of Scientific and Technical Information of China (English)

    Jadranka; Travas-Sejdic; Christian; Soeller

    2007-01-01

    1 Results Detection of biomolecules relies on a highly specific recognition event between an analyte biomolecule and a probe that is often closely connected or integrated within a sensor transducer element to provide a suitable signal. More widespread application of gene detection on a routine basis demands the development of a new generation of gene sensors that are fast, reliable and cost-effective.Conjugated polymers (CPs) have been shown to be a versatile substrate for DNA sensor construction, where...

  16. Conjugated Polymer Actuators: Prospects and Limitations

    DEFF Research Database (Denmark)

    Skaarup, Steen

    2007-01-01

    Actuators constructed with a conjugated polymer as the active part have been predicted to have a number of highly desirable properties: Large mechanical strength, high power density, i.e. high actuation speeds possible, sufficient maximum strain values, high reversibility and safe, low voltages (......-5 V), . Taking status after about 15 years of research efforts, most of these predictions have come true, the main exception being the much lower speeds actually realized in actuators....

  17. Conjugation, characterization and toxicity of lipophosphoglycan-polyacrylic acid conjugate for vaccination against leishmaniasis.

    Science.gov (United States)

    Topuzogullari, Murat; Cakir Koc, Rabia; Dincer Isoglu, Sevil; Bagirova, Melahat; Akdeste, Zeynep; Elcicek, Serhat; Oztel, Olga N; Yesilkir Baydar, Serap; Canim Ates, Sezen; Allahverdiyev, Adil M

    2013-06-03

    Research on the conjugates of synthetic polyelectrolytes with antigenic molecules, such as proteins, peptides, or carbohydrates, is an attractive area due to their highly immunogenic character in comparison to classical adjuvants. For example, polyacrylic acid (PAA) is a weak polyelectrolyte and has been used in several biomedical applications such as immunological studies, drug delivery, and enzyme immobilization. However, to our knowledge, there are no studies that document immune-stimulant properties of PAA in Leishmania infection. Therefore, we aimed to develop a potential vaccine candidate against leishmaniasis by covalently conjugating PAA with an immunologically vital molecule of lipophosphoglycan (LPG) found in Leishmania parasites. In the study, LPG and PAA were conjugated by a multi-step procedure, and final products were analyzed with GPC and MALDI-TOF MS techniques. In cytotoxicity experiments, LPG-PAA conjugates did not indicate toxic effects on L929 and J774 murine macrophage cells. We assume that LPG-PAA conjugate can be a potential vaccine candidate, and will be immunologically characterized in further studies to prove its potential.

  18. Somatostatin receptors

    DEFF Research Database (Denmark)

    Møller, Lars Neisig; Stidsen, Carsten Enggaard; Hartmann, Bolette

    2003-01-01

    therefore been acknowledged to be a third endogenous ligand at SRIF receptors. This review goes through mechanisms of signal transduction, pharmacology, and anatomical distribution of SRIF receptors. Structurally, SRIF receptors belong to the superfamily of G protein-coupled (GPC) receptors, sharing....... The generation of knock-out (KO) mice, intended as a means to define the contributions made by individual receptor subtypes, necessarily marks but an approximation. Furthermore, we must now take into account the stunning complexity of receptor co-operation indicated by the observation of receptor homo......-peptides, receptor agonists and antagonists. Relatively long half lives, as compared to those of the endogenous ligands, have been paramount from the outset. Motivated by theoretical puzzles or the shortcomings of present-day diagnostics and therapy, investigators have also aimed to produce subtype...

  19. Nanostructured conjugated polymers for photovoltaic devices

    Science.gov (United States)

    Xi, Dongjuan

    This dissertation focuses on making new systems of interdigitated bilayer structures for organic solar cells from two aspects: (i) fabricating vertically aligned semiconductor nanorod arrays by low-temperature solution process; (ii) applying the resulting nanorods arrays in solar cell devices with pre-formed or in-situ electropolymerized conjugated polymers. Two low-temperature solution methods are investigated to fabricate vertically aligned semiconductor nanorod arrays. The first method is using porous templates to prepare vertically aligned conjugated polymer nanorods arrays. In-situ anodized nanoporous alumina film is specifically designed to suspend on substrates to improve the wettability of organic solution to the alumina film, and to generate a big foot anchoring the polymer nanorods. With this specific design, vertically aligned polymer nanotube arrays with high density, 3x1010/cm2, is achieved and the nanotubes can stand vertically at the aspect ratio of 5. The second method is low-temperature direct growth of high quality semiconductor nanorod arrays without any templates by electrochemical deposition. Vertically aligned cadmium sulfide nanorod arrays are achieved by studying the growth mechanism of cadmium sulfide nanocrystal deposition and fine tuning the solution composition of the electrolyte. Chlorine doping, as a function of chlorine ion concentration in the electrolyte, modifies crystal lattice, and therefore the build-in stress, which dominates the morphology of the deposited nanocrystals as nanorods or thin films. Scanning electron microscopy, x-ray diffraction and transmission electron microscopy are applied to study the microstructures of the nanorods. Optical, electrical and field emission properties of the cadmium sulfide nanorod arrays are also studied in detail to pursue further applications of the nanorod arrays as nano-lasers and cold field emitters. Organic solar cells based on template-processed polythiophene nanotube arrays will be

  20. Biological properties of adrenomedullin conjugated with polyethylene glycol.

    Science.gov (United States)

    Kubo, Keishi; Tokashiki, Mariko; Kuwasako, Kenji; Tamura, Masaji; Tsuda, Shugo; Kubo, Shigeru; Yoshizawa-Kumagaye, Kumiko; Kato, Johji; Kitamura, Kazuo

    2014-07-01

    Adrenomedullin (AM) is a vasodilator peptide with pleiotropic effects, including cardiovascular protection and anti-inflammation. Because of these beneficial effects, AM appears to be a promising therapeutic tool for human diseases, while intravenous injection of AM stimulates sympathetic nerve activity due to short-acting potent vasodilation, resulting in increased heart rate and renin secretion. To lessen these acute reactions, we conjugated the N-terminal of human AM peptide with polyethylene glycol (PEG), and examined the biological properties of PEGylated AM in the present study. PEGylated AM stimulated cAMP production, an intracellular second messenger of AM, in cultured human embryonic kidney cells expressing a specific AM receptor in a dose-dependent manner, as did native human AM. The pEC50 value of PEGylated AM was lower than human AM, but no difference was noted in maximum response (Emax) between the PEGylated and native peptides. Intravenous bolus injection of 10nmol/kg PEGylated AM lowered blood pressure in anesthetized rats, but the acute reduction became significantly smaller by PEGylation as compared with native AM. Plasma half-life of PEGylated AM was significantly longer than native AM both in the first and second phases in rats. In summary, N-terminal PEGylated AM stimulated cAMP production in vitro, showing lessened acute hypotensive action and a prolonged plasma half-life in comparison with native AM peptide in vivo.

  1. Radiolabeled Cetuximab Conjugates for EGFR Targeted Cancer Diagnostics and Therapy

    Directory of Open Access Journals (Sweden)

    Wiebke Sihver

    2014-03-01

    Full Text Available The epidermal growth factor receptor (EGFR has evolved over years into a main molecular target for the treatment of different cancer entities. In this regard, the anti-EGFR antibody cetuximab has been approved alone or in combination with: (a chemotherapy for treatment of colorectal and head and neck squamous cell carcinoma and (b with external radiotherapy for treatment of head and neck squamous cell carcinoma. The conjugation of radionuclides to cetuximab in combination with the specific targeting properties of this antibody might increase its therapeutic efficiency. This review article gives an overview of the preclinical studies that have been performed with radiolabeled cetuximab for imaging and/or treatment of different tumor models. A particularly promising approach seems to be the treatment with therapeutic radionuclide-labeled cetuximab in combination with external radiotherapy. Present data support an important impact of the tumor micromilieu on treatment response that needs to be further validated in patients. Another important challenge is the reduction of nonspecific uptake of the radioactive substance in metabolic organs like liver and radiosensitive organs like bone marrow and kidneys. Overall, the integration of diagnosis, treatment and monitoring as a theranostic approach appears to be a promising strategy for improvement of individualized cancer treatment.

  2. Effects of mycophenolic acid-glucosamine conjugates on the base of kidney targeted drug delivery.

    Science.gov (United States)

    Wang, Xiaohong; Lin, Yan; Zeng, Yingchun; Sun, Xun; Gong, Tao; Zhang, Zhirong

    2013-11-01

    Mycophenolic acid has played an important role in treating immunosuppression and autoimmune diseases. Nevertheless, the agent needs a high dosage in treatment, following some side effects. To tackle this problem, in this study, mycophenolic acid-glucosamine conjugate (MGC), modified by 2-glucosamine, was synthesized to achieve kidney targeting and improved drug efficacy with a lower dosage. (1)H NMR, (13)C NMR and HRMS spectroscopy were used to verify the conjugate whose stability was good in vitro. The transport of MGC by human proximal renal tubular epithelial HK-2 cells was temperature-, time-, concentration-dependent and saturable, suggesting the involvement of carrier-mediated uptake. In addition, the cellular uptake of MGC dropped substantially with the inhibition of megalin receptor. The specific tissue distribution indicated the commendable renal-targeting capability of MGC. The concentration of MGC was improved in the kidney except for other tissues, about 6.76 times higher than that of MPA. Further, the bioavailability of MGC in plasma decreased as compared with mycophenolic acid. Moreover, therapeutic effect of MGC was enhanced significantly compared with MPA in the acute kidney injury model. All the findings suggested the potential of mycophenolic acid-glucosamine conjugate in kidney targeted drug delivery.

  3. Crossing the blood-brain-barrier with transferrin conjugated carbon dots: A zebrafish model study.

    Science.gov (United States)

    Li, Shanghao; Peng, Zhili; Dallman, Julia; Baker, James; Othman, Abdelhameed M; Blackwelder, Patrica L; Leblanc, Roger M

    2016-09-01

    Drug delivery to the central nervous system (CNS) in biological systems remains a major medical challenge due to the tight junctions between endothelial cells known as the blood-brain-barrier (BBB). Here we use a zebrafish model to explore the possibility of using transferrin-conjugated carbon dots (C-Dots) to ferry compounds across the BBB. C-Dots have previously been reported to inhibit protein fibrillation, and they are also used to deliver drugs for disease treatment. In terms of the potential medical application of C-Dots for the treatment of CNS diseases, one of the most formidable challenges is how to deliver them inside the CNS. To achieve this in this study, human transferrin was covalently conjugated to C-Dots. The conjugates were then injected into the vasculature of zebrafish to examine the possibility of crossing the BBB in vivo via transferrin receptor-mediated endocytosis. The experimental observations suggest that the transferrin-C-Dots can enter the CNS while C-Dots alone cannot.

  4. The determination of the rate of conjugation immunoglobuline with bifunctional chelator

    Science.gov (United States)

    Málek, Z.; Miler, V.; Budský, F.

    2006-01-01

    The work was performed under the GACR project: "Technology of preparation of radionuclides and their labelled compounds for nuclear medicine and pharmacy with the use of the reactor LVR-15" reg. no. 104/03/0499. Imaging of cell’s antigens with the use of labelled immunoglobulines allows imaging of specific receptors on cell membrane and specific tumours. It is necessary to carry out the labelling of the immunoglobulines with radionuclides of suitable physical properties, which form cations (e.g., 111In, 90Y, 177Lu) that form very strong chelates of sufficiently high stability constant preventing the dissociation of complexes or the radionuclide under “in-vivo” conditions. The immunoglobuline must be conjugated with the bifunctional chelator (BCH), which contains both chelating unit and reactive group for binding to the immunoglobuline. In our laboratory we have conjugated human IgG and monoclonal antibody CD20 with diethylenetriamine pentaacetic acid dianhydride (cDTPAA). Radionuclides 90Y and 177Lu prepared on the LVR-15 reactor in NRI Rez were used for labelling. After conjugation and labelling the yields in relation to the amount of isotopic carrier have been determined.

  5. Co-conjugation vis-à-vis individual conjugation of α-amylase and glucoamylase for hydrolysis of starch.

    Science.gov (United States)

    Jadhav, Swati B; Singhal, Rekha S

    2013-10-15

    Two enzymes, α-amylase and glucoamylase have been individually and co-conjugated to pectin by covalent binding. Both the enzyme systems showed better thermal and pH stability over the free enzyme system with the complete retention of original activities. Mixture of individually conjugated enzymes showed lower inactivation rate constant with longer half life than the co-conjugated enzyme system. Individually conjugated enzymes showed an increase of 56.48 kJ/mole and 38.22 kJ/mole in activation energy for denaturation than the free enzymes and co-conjugated enzymes, respectively. Km as well as Vmax of individually and co-conjugated enzymes was found to be higher than the free enzymes. SDS-polyacrylamide gel electrophoresis confirmed the formation of conjugate and co-conjugate as evident by increased molecular weight. Both the enzyme systems were used for starch hydrolysis where individually conjugated enzymes showed highest release of glucose at 60 °C and pH 5.0 as compared to free and co-conjugated enzyme.

  6. 177Lu-Dendrimer Conjugated to Folate and Bombesin with Gold Nanoparticles in the Dendritic Cavity: A Potential Theranostic Radiopharmaceutical

    Directory of Open Access Journals (Sweden)

    Héctor Mendoza-Nava

    2016-01-01

    Full Text Available 177Lu-labeled nanoparticles conjugated to biomolecules have been proposed as a new class of theranostic radiopharmaceuticals. The aim of this research was to synthesize 177Lu-dendrimer(PAMAM-G4-folate-bombesin with gold nanoparticles (AuNPs in the dendritic cavity and to evaluate the radiopharmaceutical potential for targeted radiotherapy and the simultaneous detection of folate receptors (FRs and gastrin-releasing peptide receptors (GRPRs overexpressed in breast cancer cells. p-SCN-Benzyl-DOTA was conjugated in aqueous-basic medium to the dendrimer. The carboxylate groups of Lys1Lys3(DOTA-bombesin and folic acid were activated with HATU and also conjugated to the dendrimer. The conjugate was mixed with 1% HAuCl4 followed by the addition of NaBH4 and purified by ultrafiltration. Elemental analysis (EDS, particle size distribution (DLS, TEM analysis, UV-Vis, and infrared and fluorescence spectroscopies were performed. The conjugate was radiolabeled using 177LuCl3 or 68GaCl3 and analyzed by radio-HPLC. Studies confirmed the dendrimer functionalization with high radiochemical purity (>95%. Fluorescence results demonstrated that the presence of AuNPs in the dendritic cavity confers useful photophysical properties to the radiopharmaceutical for optical imaging. Preliminary binding studies in T47D breast cancer cells showed a specific cell uptake (41.15±2.72%. 177Lu-dendrimer(AuNP-folate-bombesin may be useful as an optical and nuclear imaging agent for breast tumors overexpressing GRPR and FRs, as well as for targeted radiotherapy.

  7. Luminescence of a conjugated polymer containing europium (III) chelate

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Hao; Xie, Fang, E-mail: xiefang4498@126.com

    2013-12-15

    A europium (III) chelate has been incorporated in a conjugated polymer, poly-[2,2′-bipyridine-5,5′-diyl-(2,5-dihexyl-1,4-phenylene)]. From the absorbance and emission spectra measurement and using the Judd–Ofelt theory, an efficient energy transfer between the conjugated polymer and the europium (III) chelate has been confirmed. The luminescence lifetime of Eu{sup 3+} ion in the conjugated polymer is 0.352 ms and the emission cross section of this material is 3.11×10{sup −21} cm{sup 2}. -- Highlights: • A europium chelate has been incorporated in a conjugated polymer. • Energy transfer in the conjugated polymer containing europium chelate is efficient. • The conjugated polymer containing europium chelate is a promising optical material.

  8. Conjugates of abscisic acid, brassinosteroids, ethylene, gibberellins, and jasmonates.

    Science.gov (United States)

    Piotrowska, Alicja; Bajguz, Andrzej

    2011-12-01

    Phytohormones, including auxins, abscisic acid, brassinosteroids, cytokinins, ethylene, gibberellins, and jasmonates, are involved in all aspects of plant growth, and developmental processes as well as environmental responses. However, our understanding of hormonal homeostasis is far from complete. Phytohormone conjugation is considered as a part of the mechanism to control cellular levels of these compounds. Active phytohormones are changed into multiple forms by acylation, esterification or glycosylation, for example. It seems that conjugated compounds could serve as pool of inactive phytohormones that can be converted to active forms by de-conjugation reactions. Some conjugates are thought to be temporary storage forms, from which free active hormones can be released after hydrolysis. It is also believed that conjugation serves functions, such as irreversible inactivation, transport, compartmentalization, and protection against degradation. The nature of abscisic acid, brassinosteroid, ethylene, gibberellin, and jasmonate conjugates is discussed.

  9. Synthesis, characterization and biological activity of Rhein-cyclodextrin conjugate

    Science.gov (United States)

    Liu, Manshuo; Lv, Pin; Liao, Rongqiang; Zhao, Yulin; Yang, Bo

    2017-01-01

    Cyclodextrin conjugate complexation is a useful method to enhance the solubility and absorption of poorly soluble drugs. A series of new Rhein-β-cyclodextrin conjugates (Rh-CD conjugates) have been synthesized and examined. Rhein is covalently linked with the β-CD by amido linkage in a 1:1 molar ratio. The conjugates were characterized by 1H NMR, 13C NMR, HRMS, powder X-ray diffraction (powder XRD) as well as thermogravimetric analysis (TGA). The results reveal that incorporation of β-CD could improve the aqueous solubility of Rhein and the cytotoxicity against hepatocellular carcinoma (HepG2) cell line as well as antibacterial activity against three organisms. The improved biological activity and the satisfactory water solubility of the conjugates will be potentially useful for developing novel drug-cyclodextrin conjugates, such as herbal medicine.

  10. Synthesis and Evaluation of a Series of Long-Acting Glucagon-Like Peptide-1 (GLP-1) Pentasaccharide Conjugates for the Treatment of Type 2 Diabetes.

    Science.gov (United States)

    Irwin, Nigel; Patterson, Steven; de Kort, Martin; Moffett, R Charlotte; Wisse, Jeffry A J; Dokter, Wim H A; Bos, Ebo S; Miltenburg, André M M; Flatt, Peter R

    2015-08-01

    The present study details the development of a family of novel D-Ala(8) glucagon-like peptide-1 (GLP-1) peptide conjugates by site specific conjugation to an antithrombin III (ATIII) binding carrier pentasaccharide through tetraethylene glycol linkers. All conjugates were found to possess potent insulin-releasing activity. Peptides with short linkers (GLP-1 receptor (GLP-1-R) binding affinity. All D-Ala(8) GLP-1 conjugates exhibited prominent glucose-lowering action. Biological activity of the Lys(37) short-linker peptide was evident up to 72 h post-injection. In agreement, the pharmacokinetic profile of this conjugate (t1/2 , 11 h) was superior to that of the GLP-1-R agonist, exenatide. Once-daily injection of the Lys(37) short-linker peptide in ob/ob mice for 21 days significantly decreased food intake and improved HbA1c and glucose tolerance. Islet size was decreased, with no discernible change in islet number. The beneficial effects of the Lys(37) short-linker peptide were similar to or better than either exenatide or liraglutide, another GLP-1-R agonist. In conclusion, GLP-1 peptides conjugated to an ATIII binding carrier pentasaccharide have a substantially prolonged bioactive profile compatible for possible once-weekly treatment of type 2 diabetes in humans.

  11. The efficient elimination of solid tumor cells by EGFR-specific and HER2-specific scFv-SNAP fusion proteins conjugated to benzylguanine-modified auristatin F.

    Science.gov (United States)

    Woitok, Mira; Klose, Diana; Niesen, Judith; Richter, Wolfgang; Abbas, Muhammad; Stein, Christoph; Fendel, Rolf; Bialon, Magdalena; Püttmann, Christiane; Fischer, Rainer; Barth, Stefan; Kolberg, Katharina

    2016-10-28

    Antibody-drug conjugates (ADCs) combine the potency of cytotoxic drugs with the specificity of monoclonal antibodies (mAbs). Most ADCs are currently generated by the nonspecific conjugation of drug-linker reagents to certain amino acid residues in mAbs, resulting in a heterogeneous product. To overcome this limitation and prepare ADCs with a defined stoichiometry, we use SNAP-tag technology as an alternative conjugation strategy. This allows the site-specific conjugation of O(6)-benzylguanine (BG)-modified small molecules to SNAP-tag fusion proteins. To demonstrate the suitability of this system for the preparation of novel recombinant ADCs, here we conjugated SNAP-tagged single chain antibody fragments (scFvs) to a BG-modified version of auristatin F (AURIF). We used two scFv-SNAP fusion proteins targeting members of the epidermal growth factor receptor (EGFR) family that are frequently overexpressed in breast cancer. The conjugation of BG-AURIF to EGFR-specific 425(scFv)-SNAP and HER2-specific αHER2(scFv)-SNAP resulted in two potent recombinant ADCs that specifically killed breast cancer cell lines by inducing apoptosis when applied at nanomolar concentrations. These data confirm that SNAP-tag technology is a promising tool for the generation of novel recombinant ADCs.

  12. Drug resistance to chlorambucil in murine B-cell leukemic cells is overcome by its conjugation to a targeting peptide.

    Science.gov (United States)

    Gellerman, Gary; Baskin, Sophia; Galia, Luboshits; Gilad, Yosef; Firer, Michael A

    2013-02-01

    Targeting drugs through small-molecule carriers with a high affinity to receptors on cancer cells can overcome the lack of target cell specificity of most anticancer drugs. These targeted carrier-drug conjugates are also capable of reversing drug resistance in cancer cells. Although many targeted drug delivery approaches are being tested, the linkage of several and different drugs to a single carrier molecule might further enhance their therapeutic efficacy, particularly if the drugs are engineered for variable time release. This report shows that murine B-cell leukemic cells previously resistant to a chemotherapeutic drug can be made sensitive to that drug as long as it is conjugated to a targeting peptide and, in particular, when the conjugate contains multiple copies of the drug. Using a 13mer peptide (VHFFKNIVTPRTP) derived from the myelin basic protein (p-MBP), dendrimer-based peptide conjugates containing one, two, or four molecules of chlorambucil were synthesized. Although murine hybridomas expressing antibodies to either p-MBP (MBP cells) or a nonrelevant antigen (BCL-1 cells) were both resistant to free chlorambucil, exposure of the cells to the p-MBP-chlorambucil conjugate completely reversed the drug resistance in MBP, but not BCL-1 cells or normal spleen cells. Moreover, at equivalent drug doses, there was significant enhancement in the cytotoxic activity of multidrug versus single-drug copy conjugates. On the basis of these results, the use of multifunctional dendrone linkers bearing several covalently bound cytotoxic agents allows the development of more effective targeted drug systems and enhances the efficacy of currently approved drugs for B-cell leukemia.

  13. Evaluation of 64Cu-labeled bifunctional chelate-bombesin conjugates.

    Science.gov (United States)

    Ait-Mohand, Samia; Fournier, Patrick; Dumulon-Perreault, Véronique; Kiefer, Garry E; Jurek, Paul; Ferreira, Cara L; Bénard, François; Guérin, Brigitte

    2011-08-17

    Several bifunctional chelates (BFCs) were investigated as carriers of (64)Cu for PET imaging. The most widely used chelator for (64)Cu labeling of BFCs is DOTA (1,4,7,10-tetraazacyclododecane-N,N',N″,N'''-tretraacetic acid), even though this complex exhibits only moderate in vivo stability. In this study, we prepared a series of alternative chelator-peptide conjugates labeled with (64)Cu, measured in vitro receptor binding affinities in human breast cancer T47D cells expressing the gastrin-releasing peptide receptor (GRPR) and compared their in vivo stability in mice. DOTA-, NOTA-(1,4,7-triazacyclononane-1,4,7-triacetic acid), PCTA-(3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triacetic acid), and Oxo-DO3A-(1-oxa-4,7,10-triazacyclododecane-4,7,10-triacetic acid) peptide conjugates were prepared using H(2)N-Aoc-[d-Tyr(6),βAla(11),Thi(13),Nle(14)]bombesin(6-14) (BBN) as a peptide template. The BBN moiety was selected since it binds with high affinity to the GRPR, which is overexpressed on human breast cancer cells. A convenient synthetic approach for the attachment of aniline-BFC to peptides on solid support is also presented. To facilitate the attachment of the aniline-PCTA and aniline-Oxo-DO3A to the peptide via an amide bond, a succinyl spacer was introduced at the N-terminus of BBN. The partially protected aniline-BFC (p-H(2)N-Bn-PCTA(Ot-Bu)(3) or p-H(2)N-Bn-DO3A(Ot-Bu)(3)) was then coupled to the resulting N-terminal carboxylic acid preactivated with DEPBT/ClHOBt on resin. After cleavage and purification, the peptide-conjugates were labeled with (64)Cu using [(64)Cu]Cu(OAc)(2) in 0.1 M ammonium acetate buffer at 100 °C for 15 min. Labeling efficacy was >90% for all peptides; Oxo-DO3A-BBN was incubated an additional 150 min at 100 °C to achieve this high yield. Specific activities varied from 76 to 101 TBq/mmol. Competition assays on T47D cells showed that all BFC-BBN complexes retained high affinity for the GRPR. All BFC-BBN (64)Cu-conjugates

  14. Design, synthesis, characterization and study of novel conjugated polymers

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Wu [Iowa State Univ., Ames, IA (United States)

    1997-06-24

    After introducing the subject of conjugated polymers, the thesis has three sections each containing a literature survey, results and discussion, conclusions, and experimental methods on the following: synthesis, characterization of electroluminescent polymers containing conjugated aryl, olefinic, thiophene and acetylenic units and their studies for use in light-emitting diodes; synthesis, characterization and study of conjugated polymers containing silole unit in the main chain; and synthesis, characterization and study of silicon-bridged and butadiene-linked polythiophenes.

  15. Evolution of conjugation and type IV secretion systems.

    Science.gov (United States)

    Guglielmini, Julien; de la Cruz, Fernando; Rocha, Eduardo P C

    2013-02-01

    Genetic exchange by conjugation is responsible for the spread of resistance, virulence, and social traits among prokaryotes. Recent works unraveled the functioning of the underlying type IV secretion systems (T4SS) and its distribution and recruitment for other biological processes (exaptation), notably pathogenesis. We analyzed the phylogeny of key conjugation proteins to infer the evolutionary history of conjugation and T4SS. We show that single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) conjugation, while both based on a key AAA(+) ATPase, diverged before the last common ancestor of bacteria. The two key ATPases of ssDNA conjugation are monophyletic, having diverged at an early stage from dsDNA translocases. Our data suggest that ssDNA conjugation arose first in diderm bacteria, possibly Proteobacteria, and then spread to other bacterial phyla, including bacterial monoderms and Archaea. Identifiable T4SS fall within the eight monophyletic groups, determined by both taxonomy and structure of the cell envelope. Transfer to monoderms might have occurred only once, but followed diverse adaptive paths. Remarkably, some Firmicutes developed a new conjugation system based on an atypical relaxase and an ATPase derived from a dsDNA translocase. The observed evolutionary rates and patterns of presence/absence of specific T4SS proteins show that conjugation systems are often and independently exapted for other functions. This work brings a natural basis for the classification of all kinds of conjugative systems, thus tackling a problem that is growing as fast as genomic databases. Our analysis provides the first global picture of the evolution of conjugation and shows how a self-transferrable complex multiprotein system has adapted to different taxa and often been recruited by the host. As conjugation systems became specific to certain clades and cell envelopes, they may have biased the rate and direction of gene transfer by conjugation within prokaryotes.

  16. A Hybrid of DL and WYL Nonlinear Conjugate Gradient Methods

    Directory of Open Access Journals (Sweden)

    Shengwei Yao

    2014-01-01

    Full Text Available The conjugate gradient method is an efficient method for solving large-scale nonlinear optimization problems. In this paper, we propose a nonlinear conjugate gradient method which can be considered as a hybrid of DL and WYL conjugate gradient methods. The given method possesses the sufficient descent condition under the Wolfe-Powell line search and is globally convergent for general functions. Our numerical results show that the proposed method is very robust and efficient for the test problems.

  17. Synthesis and characterization of HPMA copolymer-5-FU conjugates

    Institute of Scientific and Technical Information of China (English)

    Fang Yuan; Fu Chen; Qing Yu Xiang; Xuan Qin; Zhi Rong Zhang; Yuan Huang

    2008-01-01

    N-(2-Hydroxypropyl)methacrylamide copolymer-5-fluorouracil (PHPMA-FU)conjugates were synthesized by a novel and simplified synthetic mute,and characterized by UV,FTIR and HPLC analyses.The conjugated content of 5-fluorouracil (5-FU)was 3.41 ± 0.07 wt%.The stabilities of PHPMA-FU conjugates under different conditions were studied.The results showed that HPMA copolymer was a potential carrier for tumor-targeting delivery of 5-FU.

  18. Superparamagnetic iron oxide nanoparticles conjugated with epidermal growth factor (SPION–EGF for targeting brain tumors

    Directory of Open Access Journals (Sweden)

    Shevtsov MA

    2014-01-01

    Full Text Available Maxim A Shevtsov,1,2 Boris P Nikolaev,3 Ludmila Y Yakovleva,3 Yaroslav Y Marchenko,3 Anatolii V Dobrodumov,4 Anastasiya L Mikhrina,5 Marina G Martynova,1 Olga A Bystrova,1 Igor V Yakovenko,2 Alexander M Ischenko31Institute of Cytology of the Russian Academy of Sciences (RAS, 2AL Polenov Russian Scientific Research Institute of Neurosurgery, 3Research Institute of Highly Pure Biopreparations, 4Institute of Macromolecular Compounds of the Russian Academy of Sciences (RAS, 5IM Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences (RAS, St Petersburg, RussiaAbstract: Superparamagnetic iron oxide nanoparticles (SPIONs conjugated with recombinant human epidermal growth factor (SPION–EGF were studied as a potential agent for magnetic resonance imaging contrast enhancement of malignant brain tumors. Synthesized conjugates were characterized by transmission electron microscopy, dynamic light scattering, and nuclear magnetic resonance relaxometry. The interaction of SPION–EGF conjugates with cells was analyzed in a C6 glioma cell culture. The distribution of the nanoparticles and their accumulation in tumors were assessed by magnetic resonance imaging in an orthotopic model of C6 gliomas. SPION–EGF nanosuspensions had the properties of a negative contrast agent with high coefficients of relaxation efficiency. In vitro studies of SPION–EGF nanoparticles showed high intracellular incorporation and the absence of a toxic influence on C6 cell viability and proliferation. Intravenous administration of SPION–EGF conjugates in animals provided receptor-mediated targeted delivery across the blood–brain barrier and tumor retention of the nanoparticles; this was more efficient than with unconjugated SPIONs. The accumulation of conjugates in the glioma was revealed as hypotensive zones on T2-weighted images with a twofold reduction in T2 relaxation time in comparison to unconjugated SPIONs (P<0.001. SPION

  19. Cellular uptake of folate-conjugated lipophilic superparamagnetic iron oxide nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Kyoungja [Nano-Materials Research Center, Korea Institute of Science and Technology, P. O. Box 131, Cheongryang, Seoul 130-650 (Korea, Republic of)], E-mail: kjwoo@kist.re.kr; Moon, Jihyung [Nano-Materials Research Center, Korea Institute of Science and Technology, P. O. Box 131, Cheongryang, Seoul 130-650 (Korea, Republic of); Department of Materials Science and Engineering, Korea University, 5-1, Anam-Dong, Sungbook-Ku, Seoul, 136-713 (Korea, Republic of); Choi, Kyu-Sil [Division of Molecular Imaging, Samsung Biomedical Research Institute, Samsung Medical Center, 50 Ilwon-Dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of); Seong, Tae-Yeon [Department of Materials Science and Engineering, Korea University, 5-1, Anam-Dong, Sungbook-Ku, Seoul, 136-713 (Korea, Republic of); Yoon, Kwon-Ha [Institute for Radiological Imaging Science, Wonkwang University School of Medicine, 344-2, Shinyong, Iksan, Jeonbuk 570-749 (Korea, Republic of)

    2009-05-15

    We prepared five folate-conjugated lipophilic superparamagnetic iron oxide nanoparticles (F{sub 5}-Liposuperparamagnetic iron oxide nanoparticles(SPIONs), 5.5 and 11 nm) and investigated their cellular uptake with KB cells, which is one of the representative folate-receptor over-expressing human epidermoid carcinoma cells, using MRI. The cellular uptake tests with the respective 5.5 and 11 nm F{sub 5}-LipoSPIONs at a fixed particle concentration showed appreciable amount of receptor-mediated uptakes and the specificity was higher in 5.5 nm SPIONs, due to its higher folic acid (FA) density, without inhibition. However, the numbers of the particles taken up under FA inhibition were similar, irrespective of their sizes.

  20. Multicellular computing using conjugation for wiring.

    Science.gov (United States)

    Goñi-Moreno, Angel; Amos, Martyn; de la Cruz, Fernando

    2013-01-01

    Recent efforts in synthetic biology have focussed on the implementation of logical functions within living cells. One aim is to facilitate both internal "re-programming" and external control of cells, with potential applications in a wide range of domains. However, fundamental limitations on the degree to which single cells may be re-engineered have led to a growth of interest in multicellular systems, in which a "computation" is distributed over a number of different cell types, in a manner analogous to modern computer networks. Within this model, individual cell type perform specific sub-tasks, the results of which are then communicated to other cell types for further processing. The manner in which outputs are communicated is therefore of great significance to the overall success of such a scheme. Previous experiments in distributed cellular computation have used global communication schemes, such as quorum sensing (QS), to implement the "wiring" between cell types. While useful, this method lacks specificity, and limits the amount of information that may be transferred at any one time. We propose an alternative scheme, based on specific cell-cell conjugation. This mechanism allows for the direct transfer of genetic information between bacteria, via circular DNA strands known as plasmids. We design a multi-cellular population that is able to compute, in a distributed fashion, a Boolean XOR function. Through this, we describe a general scheme for distributed logic that works by mixing different strains in a single population; this constitutes an important advantage of our novel approach. Importantly, the amount of genetic information exchanged through conjugation is significantly higher than the amount possible through QS-based communication. We provide full computational modelling and simulation results, using deterministic, stochastic and spatially-explicit methods. These simulations explore the behaviour of one possible conjugation-wired cellular computing

  1. FITC Conjugation Markedly Enhances Hepatic Clearance of N-Formyl Peptides.

    Science.gov (United States)

    Øie, Cristina Ionica; Snapkov, Igor; Elvevold, Kjetil; Sveinbjørnsson, Baldur; Smedsrød, Bård

    2016-01-01

    In both septic and aseptic inflammation, N-formyl peptides may enter the circulation and induce a systemic inflammatory response syndrome similar to that observed during septic shock. The inflammatory response is brought about by the binding of N-formyl peptide to formyl peptide receptors (FPRs), specific signaling receptors expressed on myeloid as well as non-myeloid cells involved in the inflammatory process. N-formyl peptides conjugated with fluorochromes, such as fluorescein isothiocyanate (FITC) are increasingly experimentally used to identify tissues involved in inflammation. Hypothesizing that the process of FITC-conjugation may transfer formyl peptide to a ligand that is efficiently cleared from the circulation by the natural powerful hepatic scavenging regime we studied the biodistribution of intravenously administered FITC-fNLPNTL (Fluorescein-isothiocyanate- N-Formyl-Nle-Leu-Phe-Nle-Tyr-Lys) in mice. Our findings can be summarized as follows: i) In contrast to unconjugated fNLPNTL, FITC-fNLPNTL was rapidly taken up in the liver; ii) Mouse and human liver sinusoidal endothelial cells (LSECs) and hepatocytes express formyl peptide receptor 1 (FRP1) on both mRNA (PCR) and protein (Western blot) levels; iii) Immunohistochemistry showed that mouse and human liver sections expressed FRP1 in LSECs and hepatocytes; and iv) Uptake of FITC-fNLPNTL could be largely blocked in mouse and human hepatocytes by surplus-unconjugated fNLPNTL, thereby suggesting that the hepatocytes in both species recognized FITC-fNLPNTL and fNLPNTL as indistinguishable ligands. This was in contrast to the mouse and human LSECs, in which the uptake of FITC-fNLPNTL was mediated by both FRP1 and a scavenger receptor, specifically expressed on LSECs. Based on these results we conclude that a significant proportion of FITC-fNLPNTL is taken up in LSECs via a scavenger receptor naturally expressed in these cells. This calls for great caution when using FITC-fNLPNTL and other chromogen-conjugated

  2. 2-Deoxystreptamine Conjugates by Truncation–Derivatization of Neomycin

    Directory of Open Access Journals (Sweden)

    Floris L. van Delft

    2010-03-01

    Full Text Available A small library of truncated neomycin-conjugates is prepared by consecutive removal of 2,6-diaminoglucose rings, oxidation-reductive amination of ribose, oxidation-conjugation of aminopyridine/aminoquinoline and finally dimerization. The dimeric conjugates were evaluated for antibacterial activity with a unique hemocyanin-based biosensor. Based on the outcome of these results, a second-generation set of monomeric conjugates was prepared and found to display significant antibacterial activity, in particular with respect to kanamycin-resistant E. coli.

  3. Sources and Bioactive Properties of Conjugated Dietary Fatty Acids.

    Science.gov (United States)

    Hennessy, Alan A; Ross, Paul R; Fitzgerald, Gerald F; Stanton, Catherine

    2016-04-01

    The group of conjugated fatty acids known as conjugated linoleic acid (CLA) isomers have been extensively studied with regard to their bioactive potential in treating some of the most prominent human health malignancies. However, CLA isomers are not the only group of potentially bioactive conjugated fatty acids currently undergoing study. In this regard, isomers of conjugated α-linolenic acid, conjugated nonadecadienoic acid and conjugated eicosapentaenoic acid, to name but a few, have undergone experimental assessment. These studies have indicated many of these conjugated fatty acid isomers commonly possess anti-carcinogenic, anti-adipogenic, anti-inflammatory and immune modulating properties, a number of which will be discussed in this review. The mechanisms through which these bioactivities are mediated have not yet been fully elucidated. However, existing evidence indicates that these fatty acids may play a role in modulating the expression of several oncogenes, cell cycle regulators, and genes associated with energy metabolism. Despite such bioactive potential, interest in these conjugated fatty acids has remained low relative to the CLA isomers. This may be partly attributed to the relatively recent emergence of these fatty acids as bioactives, but also due to a lack of awareness regarding sources from which they can be produced. In this review, we will also highlight the common sources of these conjugated fatty acids, including plants, algae, microbes and chemosynthesis.

  4. Site-Selective Conjugation of Native Proteins with DNA

    DEFF Research Database (Denmark)

    Trads, Julie Brender; Tørring, Thomas; Gothelf, Kurt Vesterager

    2017-01-01

    . In recent years, a number of chemical methods that target conjugation to specific sites at native proteins have become available, and an overview of these methods is provided in this Account. Our laboratory has investigated DNA-templated protein conjugation (DTPC), which offers an alternative approach...... to site-selective conjugation of DNA to proteins. The method is inspired by the concept of DNA-templated synthesis where functional groups conjugated to DNA strands are preorganized by DNA hybridization to dramatically increase the reaction rate. In DPTC, we target metal binding sites in proteins...

  5. A class of globally convergent conjugate gradient methods

    Institute of Scientific and Technical Information of China (English)

    DAI; Yuhong(戴彧虹); YUAN; Yaxiang(袁亚湘)

    2003-01-01

    Conjugate gradient methods are very important ones for solving nonlinear optimization problems,especially for large scale problems. However, unlike quasi-Newton methods, conjugate gradient methods wereusually analyzed individually. In this paper, we propose a class of conjugate gradient methods, which can beregarded as some kind of convex combination of the Fletcher-Reeves method and the method proposed byDai et al. To analyze this class of methods, we introduce some unified tools that concern a general methodwith the scalarβk having the form of φk/φk-1. Consequently, the class of conjugate gradient methods canuniformly be analyzed.

  6. Conjugated linoleic acid supplementation caused reduction of perilipin1 and aberrant lipolysis in epididymal adipose tissue

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Demin [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Li, Hongji [Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Zhou, Bo [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Han, Liqiang [Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Zhang, Xiaomei [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Yang, Guoyu, E-mail: haubiochem@163.com [Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Yang, Guoqing, E-mail: gqyang@yeah.net [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China)

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer Conjugated linoleic acid supplementation suppresses perilipin1 in epididymal fat. Black-Right-Pointing-Pointer Conjugated linoleic acid inhibits promoter activity of perilipin1 in 3T3-L1 cells. Black-Right-Pointing-Pointer Conjugated linoleic acids elevate basal but blunt hormone-stimulated lipolysis. -- Abstract: Perilipin1, a coat protein of lipid droplet, plays a key role in adipocyte lipolysis and fat formation of adipose tissues. However, it is not clear how the expression of perilipin1 is affected in the decreased white adipose tissues (WAT) of mice treated with dietary supplement of conjugated linoleic acids (CLA). Here we obtained lipodystrophic mice by dietary administration of CLA which exhibited reduced epididymal (EPI) WAT, aberrant adipocytes and decreased expression of leptin in this tissue. We found both transcription and translation of perilipin1 was suppressed significantly in EPI WAT of CLA-treated mice compared to that of control mice. The gene expression of negative regulator tumor necrosis factor {alpha} (TNF{alpha}) and the positive regulator Peroxisome Proliferator-Activated Receptor-{gamma} (PPAR{gamma}) of perilipin1 was up-regulated and down-regulated, respectively. In cultured 3T3-L1 cells the promoter activity of perilipin1 was dramatically inhibited in the presence of CLA. Using ex vivo experiment we found that the basal lipolysis was elevated but the hormone-stimulated lipolysis blunted in adipose explants of CLA-treated mice compared to that of control mice, suggesting that the reduction of perilipin1 in white adipose tissues may at least in part contribute to CLA-mediated alternation of lipolysis of WAT.

  7. Inorganic Nanoparticles Conjugated with Biofunctional Molecules

    Institute of Scientific and Technical Information of China (English)

    J.H.Choy

    2007-01-01

    1 Results We have attempted to conjugate inorganic nanoparticles with biofunctional molecules.Recently we were quite successful in demonstrating that a two-dimensional inorganic compound like layered double hydroxide (LDH),and natural and synthetic clays can be used as gene or drug delivery carriers1-4.To the best of our knowledge,such inorganic vectors are completely new and different from conventionally developed ones such as viruses and cationic liposomes,those which are limited in certain cases of ap...

  8. Excitons in conjugated polymers from first principles

    Science.gov (United States)

    van der Horst, J.-W.; Bobbert, P. A.; Pasveer, W. F.; Michels, M. A. J.; Brocks, G.; Kelly, P. J.

    2002-08-01

    By a combination of ab-initio computational techniques, based on density-functional theory, GW theory, and the Bethe-Salpeter equation, we study the opto-electronic properties of several conjugated polymers and in particular the properties of excitons. We study three different situations: (I) an isolated polymer chain, (II) a chain embedded in a dielectric medium, and (III) a polymer crystal. Surprisingly, the results obtained for situation (II) generally agree best with experiment. We discuss possible reasons for this rule and an interesting exception.

  9. Interplay of alternative conjugated pathways and steric interactions on the electronic and optical properties of donor-acceptor conjugated polymers

    KAUST Repository

    Lima, Igo T.

    2014-01-01

    Donor-acceptor π-conjugated copolymers are of interest for a wide range of electronic applications, including field-effect transistors and solar cells. Here, we present a density functional theory (DFT) study of the impact of varying the conjugation pathway on the geometric, electronic, and optical properties of donor-acceptor systems. We consider both linear ("in series"), traditional conjugation among the donor-acceptor moieties versus structures where the acceptor units are appended orthogonally to the linear, donor-only conjugated backbone. Long-range-corrected hybrid functionals are used in the investigation with the values of the tuned long-range separation parameters providing an estimate of the extent of conjugation as a function of the oligomer architecture. Considerable differences in the electronic and optical properties are determined as a function of the nature of the conjugation pathway, features that should be taken into account in the design of donor-acceptor copolymers.

  10. Evaluation of Haemophilus influenzae Type B Conjugate Vaccine (Meningococcal Protein Conjugate in Canadian Infants

    Directory of Open Access Journals (Sweden)

    David W Scheifele

    1994-01-01

    Full Text Available Objective: To assess adverse effects and immune responses with a three-dose series of Haemophilus influenzae type b meningococcal protein conjugate (PedvaxHIB or Hib.OMP vaccine, including any immunological response alterations from concurrent administration with routine vaccines for infants.

  11. Radionuclide conjugates of calcitonin for imaging bone disease and cancer

    Energy Technology Data Exchange (ETDEWEB)

    Greenland, William Edward Peverell

    2002-07-01

    Salmon calcitonin (sCt) is a peptide with a higher affinity for human calcitonin receptors (hCtR) than human calcitonin. It has been used for treating osteoporosis, Paget's disease and bone pain. High levels of hCtRs are expressed on osteoclasts, bone metastases and primary breast and prostate cancers. The peptide was chosen for radiolabelling as a possible imaging agent. Direct labelling with {sup 99m}Tc via simultaneous reduction of the indigenous disulfide bond and {sup 99m}TcO{sub 4}{sup -} (VII) with the water soluble phenyl phosphine (TPPDS) was performed. The radiolabelled peptide was not suitable for use as a radiopharmaceutical due to the heterogeneity of the product as observed by reverse phase HPLC and due to poor binding to the human breast cancer cell line MCF7. The electospray MS suggested a {sup 99}Tc-TPPDS (III) core instead of the expected {sup 99}Tc=O (V) core. Normal sCt has 3 conjugatible primary amines leading to a mixture of 8 possible products. A sCt analogue (sCtA) with a single primary amine was produced and conjugated to the chelator TETA to produce a single conjugated species. The sCtA-TETA was labelled with cold Cu and characterised by electospray MS. The monodentate ligand Hynic was synthesised directly into the peptide using N-{alpha}-Fmoc-N-{epsilon}-(Hynic-Boc)-Lys a novel orthogonally protected amino acid. The peptide was labelled with {sup 99m}Tc with tricine coligands. The radiolabelled peptide produced a single peak as observed by reverse phase HPLC and bound to MCF7 cell in a specific manner. The electospray MS suggested that one of the tricine coligands is lost due to the heating effect and possibly replaced by an adjacent histidine acting as a ternary ligand. The sCtLys{sup 18}-Hynic{sup 99m}Tc(tricine){sub 2} labelled peptide is the lead radiolabelled peptide and could be used for a normal biodistribution animal study, followed by clinical evaluation in humans. (author)

  12. Early detection of breast cancer: a molecular optical imaging approach using novel estrogen conjugate fluorescent dye

    Science.gov (United States)

    Bhattacharjee, Shubhadeep; Jose, Iven

    2011-02-01

    Estrogen induced proliferation of mutant cells is widely understood to be the one of major risk determining factor in the development of breast cancer. Hence determination of the Estrogen Receptor[ER] status is of paramount importance if cancer pathogenesis is to be detected and rectified at an early stage. Near Infrared Fluorescence [NIRf] Molecular Optical Imaging is emerging as a powerful tool to monitor bio-molecular changes in living subjects. We discuss pre-clinical results in our efforts to develop an optical imaging diagnostic modality for the early detection of breast cancer. We have successfully carried out the synthesis and characterization of a novel target-specific NIRf dye conjugate aimed at measuring Estrogen Receptor[ER] status. The conjugate was synthesized by ester formation between 17-β estradiol and a hydrophilic derivative of Indocyanine Green (ICG) cyanine dye, bis-1,1-(4-sulfobutyl) indotricarbocyanine-5-carboxylic acid, sodium salt. In-vitro studies regarding specific binding and endocytocis of the dye performed on ER+ve [MCF-7] and control [MDA-MB-231] adenocarcinoma breast cancer cell lines clearly indicated nuclear localization of the dye for MCF-7 as compared to plasma level staining for MDA-MB-231. Furthermore, MCF-7 cells showed ~4.5-fold increase in fluorescence signal intensity compared to MDA-MB-231. A 3-D mesh model mimicking the human breast placed in a parallel-plate DOT Scanner is created to examine the in-vivo efficacy of the dye before proceeding with clinical trials. Photon migration and florescence flux intensity is modeled using the finite-element method with the coefficients (quantum yield, molar extinction co-efficient etc.) pertaining to the dye as obtained from photo-physical and in-vitro studies. We conclude by stating that this lipophilic dye can be potentially used as a target specific exogenous contrast agent in molecular optical imaging for early detection of breast cancer.

  13. Targeting Mast Cells and Basophils with Anti-FcεRIα Fab-Conjugated Celastrol-Loaded Micelles Suppresses Allergic Inflammation.

    Science.gov (United States)

    Peng, Xia; Wang, Juan; Li, Xianyang; Lin, Lihui; Xie, Guogang; Cui, Zelin; Li, Jia; Wang, Yuping; Li, Li

    2015-12-01

    Mast cells and basophils are effector cells in the pathophysiology of allergic diseases. Targeted elimination of these cells may be a promising strategy for the treatment of allergic disorders. Our present study aims at targeted delivery of anti-FcεRIα Fab-conjugated celastrol-loaded micelles toward FcεRIα receptors expressed on mast cells and basophils to have enhanced anti-allergic effect. To achieve this aim, we prepared celastrol-loaded (PEO-block-PPO-block-PEO, Pluronic) polymeric nanomicelles using thin-film hydration method. The anti-FcεRIα Fab Fragment was then conjugated to carboxyl groups on drug-loaded micelles via EDC amidation reaction. The anti-FcεRIα Fab-conjugated celastrol-loaded micelles revealed uniform particle size (93.43 ± 12.93 nm) with high loading percentage (21.2 ± 1.5% w/w). The image of micelles showed oval and rod like. The anti-FcεRIα Fab-conjugated micelles demonstrated enhanced cellular uptake and cytotoxity toward target KU812 cells than non-conjugated micelles in vitro. Furthermore, diffusion of the drug into the cells allowed an efficient induction of cell apoptosis. In mouse model of allergic asthma, treatment with anti-FcεRIα Fab-conjugated micelles increased lung accumulation of micelles, and significantly reduced OVA-sIgE, histamine and Th2 cytokines (IL-4, IL-5, TNF-α) levels, eosinophils infiltration and mucus production. In addition, in mouse model of passive cutaneous anaphylaxis, anti-FcεRIα Fab-conjugated celastrol-loaded micelles treatment significantly decreased extravasated evan's in the ear. These results indicate that anti-FcεRIα Fab-conjugated celastrol-loaded micelles can target and selectively kill mast cells and basophils which express FcεRIα, and may be efficient reagents for the treatment of allergic disorders and mast cell related diseases.

  14. Trimellitic anhydride-conjugated serum albumin activates rat alveolar macrophages in vitro

    Directory of Open Access Journals (Sweden)

    Bloksma Nanne

    2006-06-01

    Full Text Available Abstract Background Occupational exposure to airborne low molecular weight chemicals, like trimellitic anhydride (TMA, can result in occupational asthma. Alveolar macrophages (AMs are among the first cells to encounter these inhaled compounds and were previously shown to influence TMA-induced asthma-like symptoms in the Brown Norway rat. TMA is a hapten that will bind to endogenous proteins upon entrance of the body. Therefore, in the present study we determined if TMA and TMA conjugated to serum albumin induced the production of the macrophage mediators nitric oxide (NO, tumour necrosis factor (TNF, and interleukin 6 (IL-6 in vitro using the rat AM cell line NR8383 and primary AMs derived from TMA-sensitized and naïve Brown Norway rats. Methods Cells were incubated with different concentrations of TMA, TMA conjugated to bovine serum albumin (BSA, and BSA as a control for 24 h and the culture supernatant was analyzed for mediator content. Results TMA alone was not able to induce the production of mediators by NR8383 cells and primary AMs from sensitized and sham-treated rats. TMA-BSA, on the contrary, dose-dependently stimulated the production of NO, TNF, and IL-6 by NR8383 cells and of NO and TNF, but not IL-6, by primary AMs independent of sensitization. Conclusion Results suggest that although TMA is a highly reactive compound, conjugation to a suitable protein is necessary to induce mediator production by AMs. Furthermore, the observation that effects of TMA-BSA were independent of sensitization suggests involvement of an immunologically non-specific receptor. In the discussion it is argued that a macrophage scavenger receptor is a likely candidate.

  15. Recent Findings Concerning PAMAM Dendrimer Conjugates with Cyclodextrins as Carriers of DNA and RNA

    Directory of Open Access Journals (Sweden)

    Keiichi Motoyama

    2009-08-01

    Full Text Available We have evaluated the potential use of various polyamidoamine (PAMAM dendrimer [dendrimer, generation (G 2-4] conjugates with cyclodextrins (CyDs as novel DNA and RNA carriers. Among the various dendrimer conjugates with CyDs, the dendrimer (G3 conjugate with α-CyD having an average degree of substitution (DS of 2.4 [α-CDE (G3, DS2] displayed remarkable properties as DNA, shRNA and siRNA delivery carriers through the sensor function of α-CDEs toward nucleic acid drugs, cell surface and endosomal membranes. In an attempt to develop cell-specific gene transfer carriers, we prepared sugar-appended α-CDEs. Of the various sugar-appended α-CDEs prepared, galactose- or mannose-appended α-CDEs provided superior gene transfer activity to α-CDE in various cells, but not cell-specific gene delivery ability. However, lactose-appended α-CDE [Lac-α-CDE (G2] was found to possess asialoglycoprotein receptor (AgpR-mediated hepatocyte-selective gene transfer activity, both in vitro and in vivo. Most recently, we prepared folate-poly(ethylene glycol-appended α-CDE [Fol-PαC (G3] and revealed that Fol-PαC (G3 imparted folate receptor (FR-mediated cancer cell-selective gene transfer activity. Consequently, α-CDEs bearing integrated, multifunctional molecules may possess the potential to be novel carriers for DNA, shRNA and siRNA.

  16. [Pneumococcal vaccines. New conjugate vaccines for adults].

    Science.gov (United States)

    Campins Martí, Magda

    2015-11-01

    Pneumococcal infections are a significant cause of morbidity and mortality, and are one of the 10 leading causes of death worldwide. Children under 2 years have a higher incidence rate, followed by adults over 64 years. The main risk group are individuals with immunodeficiency, and those with anatomical or functional asplenia, but can also affect immunocompetent persons with certain chronic diseases. Significant progress has been made in the last 10 years in the prevention of these infections. Until a few years ago, only the 23-valent non-conjugate pneumococcal vaccine was available. Its results were controversial in terms of efficacy and effectiveness, and with serious limitations on the type of immune response induced. The current possibility of using the 13-valent conjugate vaccine in adults has led to greater expectations in improving the prevention of pneumococcal disease in these age groups. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  17. Enhancement of intracellular concentration and biological activity of PNA after conjugation with a cell-penetrating synthetic model peptide.

    Science.gov (United States)

    Oehlke, Johannes; Wallukat, Gerd; Wolf, Yvonne; Ehrlich, Angelika; Wiesner, Burkhard; Berger, Hartmut; Bienert, Michael

    2004-07-01

    In order to evaluate the ability of the cell-penetrating alpha-helical amphipathic model peptide KLALKLALKALKAALKLA-NH(2) (MAP) to deliver peptide nucleic acids (PNAs) into mammalian cells, MAP was covalently linked to the 12-mer PNA 5'-GGAGCAGGAAAG-3' directed against the mRNA of the nociceptin/orphanin FQ receptor. The cellular uptake of both the naked PNA and its MAP-conjugate was studied by means of capillary electrophoresis combined with laser-induced fluorescence detection, confocal laser scanning microscopy and fluorescence-activated cell sorting. Incubation with the fluorescein-labelled PNA-peptide conjugate led to three- and eightfold higher intracellular concentrations in neonatal rat cardiomyocytes and CHO cells, respectively, than found after exposure of the cells to the naked PNA. Correspondingly, pretreatment of spontaneously-beating neonatal rat cardiomyocytes with the PNA-peptide conjugate and the naked PNA slowed down the positive chronotropic effect elicited by the neuropeptide nociceptin by 10- and twofold, respectively. The main reasons for the higher bioavailability of the PNA-peptide conjugate were found to be a more rapid cellular uptake in combination with a lowered re-export and resistance against influences of serum.

  18. Interaction of sulfonylurea-conjugated polymer with insulinoma cell line of MIN6 and its effect on insulin secretion.

    Science.gov (United States)

    Park, K H; Kim, S W; Bae, Y H

    2001-04-01

    A carboxylated derivative of sulfonylurea (SU), an insulinotropic agent, was synthesized and grafted onto a water-soluble polymer as a biospecific and stimulating polymer for insulin secretion. To evaluate the effect of the SU-conjugated polymer on insulin secretion, its solution in dimethyl sulfoxide was added to the culture of insulinoma cell line of MIN6 cells to make 10 nM of SU units in the medium and incubated for 3 h at 37 degrees C. The culture medium was conditioned with glucose concentration of 3.3 or 25 mM. To verify the specific interaction between the SU (K+ channel closer)-conjugated polymer and MIN6 cells, the cells were pretreated with diazoxide, an agonist of adenosine triphosphate-sensitive K+ channel (K+ channel opener), before adding the SU-conjugated polymer to the cell culture medium. This treatment suppressed the action of SUs on MIN6 cells. Fluorescence-labeled polymer with rodamine-B isothiocyanate was used to visualize the interactions, and we found that the labeled polymer strongly absorbed to MIN6 cells, probably owing to its specific interaction mediated by SU receptors on the cell membrane. The fluorescence intensity on the cells significantly increased with an increase in incubation time and polymer concentration. A confocal laser microscopic study further confirmed this interaction. The results from this study provided evidence that SU-conjugated copolymer stimulates insulin secretion by specific interactions of SU moieties in the polymer with MIN6 cells.

  19. Folate/NIR 797-conjugated albumin magnetic nanospheres: synthesis, characterisation, and in vitro and in vivo targeting evaluation.

    Directory of Open Access Journals (Sweden)

    Qiusha Tang

    Full Text Available A practical and effective strategy for synthesis of Folate-NIR 797-conjugated Magnetic Albumin Nanospheres (FA-NIR 797-MAN was developed. For this strategy, Magnetic Albumin Nanospheres (MAN, composed of superparamagnetic iron oxide nanoparticles (SPIONs and bovine serum albumin (BSA, were covalently conjugated with folic acid (FA ligands to enhance the targeting capability of the particles to folate receptor (FR over-expressing tumours. Subsequently, a near-infrared (NIR fluorescent dye NIR 797 was conjugated with FA-conjugated MAN for in vivo fluorescence imaging. The FA-NIR 797-MAN exhibited low toxicity to a human nasopharyngeal epidermal carcinoma cell line (KB cells. Additionally, in vitro and in vivo evaluation of the dynamic behaviour and targeting ability of FA-NIR 797-MAN to KB tumours validated the highly selective affinity of FA-NIR 797-MAN for FR-positive tumours. In summary, the FA-NIR 797-MAN prepared here exhibited great potential for tumour imaging, since the near-infrared fluorescence contrast agents target cells via FR-mediated endocytosis. The high fluorescence intensity together with the targeting effect makes FA-NIR 797-MAN a promising candidate for imaging, monitoring, and early diagnosis of cancer at the molecular and cellular levels.

  20. Enhanced Peptide Stability Against Protease Digestion Induced by Intrinsic Factor Binding of a Vitamin B12 Conjugate of Exendin-4.

    Science.gov (United States)

    Bonaccorso, Ron L; Chepurny, Oleg G; Becker-Pauly, Christoph; Holz, George G; Doyle, Robert P

    2015-09-08

    Peptide digestion from proteases is a significant limitation in peptide therapeutic development. It has been hypothesized that the dietary pathway of vitamin B12 (B12) may be exploited in this area, but an open question is whether B12-peptide conjugates bound to the B12 gastric uptake protein intrinsic factor (IF) can provide any stability against proteases. Herein, we describe a new conjugate of B12 with the incretin peptide exendin 4 that demonstrates picomolar agonism of the glugacon-like peptide-1 receptor (GLP1-R). Stability studies reveal that Ex-4 is digested by pancreatic proteases trypsin and chymotrypsin and by the kidney endopeptidase meprin β. Prebinding the B12 conjugate to IF, however, resulted in up to a 4-fold greater activity of the B12-Ex-4 conjugate relative to Ex-4, when the IF-B12-Ex-4 complex was exposed to 22 μg/mL of trypsin, 2.3-fold greater activity when exposed to 1.25 μg/mL of chymotrypsin, and there was no decrease in function at up to 5 μg/mL of meprin β.

  1. Folate/NIR 797-conjugated albumin magnetic nanospheres: synthesis, characterisation, and in vitro and in vivo targeting evaluation.

    Science.gov (United States)

    Tang, Qiusha; An, Yanli; Liu, Dongfang; Liu, Peidang; Zhang, Dongsheng

    2014-01-01

    A practical and effective strategy for synthesis of Folate-NIR 797-conjugated Magnetic Albumin Nanospheres (FA-NIR 797-MAN) was developed. For this strategy, Magnetic Albumin Nanospheres (MAN), composed of superparamagnetic iron oxide nanoparticles (SPIONs) and bovine serum albumin (BSA), were covalently conjugated with folic acid (FA) ligands to enhance the targeting capability of the particles to folate receptor (FR) over-expressing tumours. Subsequently, a near-infrared (NIR) fluorescent dye NIR 797 was conjugated with FA-conjugated MAN for in vivo fluorescence imaging. The FA-NIR 797-MAN exhibited low toxicity to a human nasopharyngeal epidermal carcinoma cell line (KB cells). Additionally, in vitro and in vivo evaluation of the dynamic behaviour and targeting ability of FA-NIR 797-MAN to KB tumours validated the highly selective affinity of FA-NIR 797-MAN for FR-positive tumours. In summary, the FA-NIR 797-MAN prepared here exhibited great potential for tumour imaging, since the near-infrared fluorescence contrast agents target cells via FR-mediated endocytosis. The high fluorescence intensity together with the targeting effect makes FA-NIR 797-MAN a promising candidate for imaging, monitoring, and early diagnosis of cancer at the molecular and cellular levels.

  2. Quantum-dot-conjugated graphene as a probe for simultaneous cancer-targeted fluorescent imaging, tracking, and monitoring drug delivery.

    Science.gov (United States)

    Chen, Mei-Ling; He, Ye-Ju; Chen, Xu-Wei; Wang, Jian-Hua

    2013-03-20

    We report a novel quantum-dot-conjugated graphene, i.e., hybrid SiO2-coated quantum dots (HQDs)-conjugated graphene, for targeted cancer fluorescent imaging, tracking, and monitoring drug delivery, as well as cancer therapy. The hybrid SiO2 shells on the surface of QDs not only mitigate its toxicity, but also protect its fluorescence from being quenched by graphene. By functionalizing the surface of HQDs-conjugated graphene (graphene-HQDs) with transferrin (Trf), we developed a targeted imaging system capable of differential uptake and imaging of cancer cells that express the Trf receptor. The widely used fluorescent antineoplastic anthracycline drug, doxorubicin (DOX), is adsorbed on the surface of graphene and results in a large loading capacity of 1.4 mg mg(-1). It is advantageous that the new delivery system exhibits different fluorescence color in between graphene-HQDs and DOX in the aqueous core upon excitation at a same wavelength for the purpose of tracking and monitoring drug delivery. This simple multifunctional nanoparticle system can deliver DOX to the targeted cancer cells and enable us to localize the graphene-HQDs and monitor intracellular DOX release. The specificity and safety of the nanoparticle conjugate for cancer imaging, monitoring, and therapy has been demonstrated in vitro.

  3. 78 FR 18999 - Prospective Grant of Start-Up Exclusive License: Photosensitizing Antibody-Fluorophore Conjugates...

    Science.gov (United States)

    2013-03-28

    ...: Photosensitizing Antibody-Fluorophore Conjugates for Photoimmunotherapy AGENCY: National Institutes of Health...-01), and entitled ``Photosensitizing Antibody- Fluorophore Conjugates,'' to Aspyrian Therapeutics.... The field of use may be limited to ``use of photosensitizing antibody-fluorophore conjugate by...

  4. Preparation and characterization of microspheres of albumin-heparin conjugates

    NARCIS (Netherlands)

    Kwon, Glen S.; Bae, You Han; Kim, Sung Wan; Cremers, Harry; Feijen, Jan

    1991-01-01

    Albumin-heparin microspheres have been prepared as a new drug carrier. A soluble albumin-heparin conjugate was synthesized by forming amide bonds between human serum albumin and heparin. After purification the albumin-heparin conjugate was crosslinked in a water-in-oil emulsion to form albumin-hepar

  5. Comparative study of the three different fluorophore antibody conjugation strategies.

    Science.gov (United States)

    Shrestha, Dilip; Bagosi, Adrienn; Szöllősi, János; Jenei, Attila

    2012-09-01

    The progression in bioconjugational chemistry has significantly contributed to the evolution and success of protein biology. Mainly, antibody chemistry has been a subject of intensive study owing to the expansion of research areas warranted by using various derivatives of conjugated antibodies. Three reactive moieties (amine, sulfhydryl and carbohydrate) in the antibodies are chiefly favored for the conjugational purpose. This feature is known for decades, nevertheless, amine based conjugation is still the most preferred strategy despite the appreciation the other two methods receive in conserving the antigen binding affinity (ABA). No single report has been published, according to our knowledge, where these three conjugation strategies were applied to the same fluorophore antibody systems. In this study, we evaluated conjugation yield, time demand and cost efficiency of these conjugation procedures. Our results showed that amine based conjugations was by far the best technique due to its simplicity, rapidity, ease of operation, higher conjugate yield, cheaper cost and potential for larger fluorophore/protein labeling ratio without having much effect in ABA. Furthermore, sulfhydryl labeling clearly excelled in terms of reduced non-specific binding and mild effect in ABA but was usually complicated by an asymmetric antibody reduction due to mercaptoethylamine while carbohydrate oxidation based strategy performed the worst during our experiment.

  6. Heat shock increases conjugation efficiency in Clostridium difficile.

    Science.gov (United States)

    Kirk, Joseph A; Fagan, Robert P

    2016-12-01

    Clostridium difficile infection has increased in incidence and severity over the past decade, and poses a unique threat to human health. However, genetic manipulation of C. difficile remains in its infancy and the bacterium remains relatively poorly characterised. Low-efficiency conjugation is currently the only available method for transfer of plasmid DNA into C. difficile. This is practically limiting and has slowed progress in understanding this important pathogen. Conjugation efficiency varies widely between strains, with important clinically relevant strains such as R20291 being particularly refractory to plasmid transfer. Here we present an optimised conjugation method in which the recipient C. difficile is heat treated prior to conjugation. This significantly improves conjugation efficiency in all C. difficile strains tested including R20291. Conjugation efficiency was also affected by the choice of media on which conjugations were performed, with standard BHI media giving most transconjugant recovery. Using our optimised method greatly increased the ease with which the chromosome of R20291 could be precisely manipulated by homologous recombination. Our method improves on current conjugation protocols and will help speed genetic manipulation of strains otherwise difficult to work with. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. CONVERGENCE PROPERTIES OF THE DEPENDENT PRP CONJUGATE GRADIENT METHODS

    Institute of Scientific and Technical Information of China (English)

    Shujun LIAN; Changyu WANG; Lixia CAO

    2006-01-01

    In this paper, a new region of βκ with respect to βPRPκ is given. With two Armijo-type line searches, the authors investigate the global convergence properties of the dependent PRP conjugate gradient methods, which extend the global convergence results of PRP conjugate gradient method proved by Grippo and Lucidi (1997) and Dai and Yuan (2002).

  8. Opto-electronic properties of charged conjugated molecules

    NARCIS (Netherlands)

    Fratiloiu, S.

    2007-01-01

    The aim of this thesis is to provide fundamental insight into the nature and opto-electronic properties of charge carriers on conjugated oligomers and polymers. Electronic structure, optical absorption properties and distribution of charge carriers along the chains of different conjugated materials

  9. Fabrication of Conjugated Polymer Nanowires by Edge Lithography

    NARCIS (Netherlands)

    Lipomi, Darren J.; Chiechi, Ryan C.; Dickey, Michael D.; Whitesides, George M.

    2008-01-01

    This paper describes the fabrication of conjugated polymer nanowires by a three stage process: (i) spin-coating a composite film comprising alternating layers of a conjugated polymer and a sacrificial material, (ii) embedding the film in an epoxy matrix and sectioning it with an ultramicrotome

  10. A NONMONOTONE CONJUGATE GRADIENT ALGORITHM FOR UNCONSTRAINED OPTIMIZATION

    Institute of Scientific and Technical Information of China (English)

    DAI Yuhong

    2002-01-01

    Conjugate gradient methods are very important methods for unconstrained optimization, especially for large scale problems. In this paper, we propose a new conjugate gradient method, in which the technique of nonmonotone line search is used. Under mild assumptions, we prove the global convergence of the method. Some numerical results are also presented.

  11. Prostaglandin phospholipid conjugates with unusual biophysical and cytotoxic properties

    DEFF Research Database (Denmark)

    Pedersen, Palle Jacob; Adolph, Sidsel K.; Andresen, Thomas Lars;

    2010-01-01

    The synthesis of two secretory phospholipase A(2) IIA sensitive 15-deoxy-Delta(12,14)-prostaglandin J(2) phospholipid conjugates is described and their biophysical and biological properties are reported. The conjugates spontaneously form particles in the liposome size region upon dispersion in an...

  12. Design, synthesis and preliminary evaluation of dopamine-amino acid conjugates as potential D1 dopaminergic modulators.

    Science.gov (United States)

    Tutone, Marco; Chinnici, Aurora; Almerico, Anna Maria; Perricone, Ugo; Sutera, Flavia Maria; De Caro, Viviana

    2016-11-29

    The dopamine-amino acid conjugate DA-Phen was firstly designed to obtain a useful prodrug for the therapy of Parkinson's disease, but experimental evidence shows that it effectively interacts with D1 dopamine receptors (D1DRs), leading to an enhancement in cognitive flexibility and to the development of adaptive strategies in aversive mazes, together with a decrease in despair-like behavior. In this paper, homology modelling, molecular dynamics, and site mapping of D1 receptor were carried out with the aim of further performing docking studies on other dopamine conjugates compared with D1 agonists, in the attempt to identify new compounds with potential dopaminergic activity. Two new conjugates (DA-Trp 2C, and DA-Leu 3C) have been identified as the most promising candidates, and consequently synthesized. Preliminary evaluation in terms of distribution coefficient (D(pH7.4)), stability in rat brain homogenate, and in human plasma confirmed that DA-Trp (2C), and DA-Leu (3C) could be considered as very valuable candidates for further in vivo studies as new dopaminergic drugs. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. Atomic force microscopy recognition of protein A on Staphylococcus aureus cell surfaces by labelling with IgG–Au conjugates

    Directory of Open Access Journals (Sweden)

    Elena B. Tatlybaeva

    2013-11-01

    Full Text Available The labelling of functional molecules on the surface of bacterial cells is one way to recognize the bacteria. In this work, we have developed a method for the selective labelling of protein A on the cell surfaces of Staphylococcus aureus by using nanosized immunogold conjugates as cell-surface markers for atomic force microscopy (AFM. The use of 30-nm size Au nanoparticles conjugated with immunoglobulin G (IgG allowed the visualization, localization and distribution of protein A–IgG complexes on the surface of S. aureus. The selectivity of the labelling method was confirmed in mixtures of S. aureus with Bacillus licheniformis cells, which differed by size and shape and had no IgG receptors on the surface. A preferential binding of the IgG–Au conjugates to S. aureus was obtained. Thus, this novel approach allows the identification of protein A and other IgG receptor-bearing bacteria, which is useful for AFM indication of pathogenic microorganisms in poly-component associations.

  14. Genetic Drift Suppresses Bacterial Conjugation in Spatially Structured Populations

    Science.gov (United States)

    Freese, Peter D.; Korolev, Kirill S.; Jiménez, José I.; Chen, Irene A.

    2014-02-01

    Conjugation is the primary mechanism of horizontal gene transfer that spreads antibiotic resistance among bacteria. Although conjugation normally occurs in surface-associated growth (e.g., biofilms), it has been traditionally studied in well-mixed liquid cultures lacking spatial structure, which is known to affect many evolutionary and ecological processes. Here we visualize spatial patterns of gene transfer mediated by F plasmid conjugation in a colony of Escherichia coli growing on solid agar, and we develop a quantitative understanding by spatial extension of traditional mass-action models. We found that spatial structure suppresses conjugation in surface-associated growth because strong genetic drift leads to spatial isolation of donor and recipient cells, restricting conjugation to rare boundaries between donor and recipient strains. These results suggest that ecological strategies, such as enforcement of spatial structure and enhancement of genetic drift, could complement molecular strategies in slowing the spread of antibiotic resistance genes.

  15. Responsive Guest Encapsulation of Dynamic Conjugated Microporous Polymers.

    Science.gov (United States)

    Xu, Lai; Li, Youyong

    2016-06-30

    The host-guest complexes of conjugated microporous polymers encapsulating C60 and dye molecules have been investigated systematically. The orientation of guest molecules inside the cavities, have different terms: inside the open cavities of the polymer, or inside the cavities formed by packing different polymers. The host backbone shows responsive dynamic behavior in order to accommodate the size and shape of incoming guest molecule or guest aggregates. Simulations show that the host-guest binding of conjugated polymers is stronger than that of non-conjugated polymers. This detailed study could provide a clear picture for the host-guest interaction for dynamic conjugated microporous polymers. The mechanism obtained could guide designing new conjugated microporous polymers.

  16. Design of Self-Assembling Protein-Polymer Conjugates.

    Science.gov (United States)

    Carter, Nathan A; Geng, Xi; Grove, Tijana Z

    Protein-polymer conjugates are of particular interest for nanobiotechnology applications because of the various and complementary roles that each component may play in composite hybrid-materials. This chapter focuses on the design principles and applications of self-assembling protein-polymer conjugate materials. We address the general design methodology, from both synthetic and genetic perspective, conjugation strategies, protein vs. polymer driven self-assembly and finally, emerging applications for conjugate materials. By marrying proteins and polymers into conjugated bio-hybrid materials, materials scientists, chemists, and biologists alike, have at their fingertips a vast toolkit for material design. These inherently hierarchical structures give rise to useful patterning, mechanical and transport properties that may help realize new, more efficient materials for energy generation, catalysis, nanorobots, etc.

  17. Protein conjugation with PAMAM nanoparticles: Microscopic and thermodynamic analysis.

    Science.gov (United States)

    Chanphai, P; Froehlich, E; Mandeville, J S; Tajmir-Riahi, H A

    2017-02-01

    PAMAM dendrimers form strong protein conjugates that are used in drug delivery systems. We report the thermodynamic and binding analysis of polyamidoamine (PAMAM-G4) conjugation with human serum albumin (HSA), bovine serum albumin (BSA) and milk beta-lactoglobulin (b-LG) in aqueous solution at physiological pH. Hydrophobicity played a major role in PAMAM-protein interactions with more hydrophobic b-LG forming stronger polymer-protein conjugates. Thermodynamic parameters showed PAMAM-protein bindings occur via hydrophobic and H-bonding contacts for b-LG, while van der waals and H-bonding interactions prevail in HSA and BSA-polymer conjugates. The protein loading efficacy was 45-55%. PAMAM complexation induced major alterations of protein conformation. TEM images show major polymer morphological changes upon protein conjugation.

  18. In vitro biological properties of flavonoid conjugates found in vivo.

    Science.gov (United States)

    Williamson, G; Barron, D; Shimoi, K; Terao, J

    2005-05-01

    For some flavonoids such as quercetin, isoflavones and catechins, the pathways of absorption and metabolism are now reasonably well characterised and understood. By definition, for biological activity of flavonoids to be manifest, the target tissue, which includes the blood and vascular system, must respond to the form(s) of flavonoid that it encounters. Bioavailability studies have shown that the circulating form of most flavonoids is as conjugates, with a few notable exceptions. There have been several recent papers on the in vitro biological properties of conjugates that have been found in vivo. This paper reviews the properties of these conjugates. Most of the information currently available is on quercetin glucuronides, but also on isoflavone and catechin conjugates. In addition to the biological properties of the conjugates, the partition coefficients and methods of synthesis are also presented.

  19. A Comparative Study of Two Folate-Conjugated Gold Nanoparticles for Cancer Nanotechnology Applications

    Energy Technology Data Exchange (ETDEWEB)

    Mansoori, G. Ali, E-mail: mansoori@uic.edu; Brandenburg, Kenneth S. [Department of Bioengineering, University of Illinois at Chicago, 851 S. Morgan St. (MC 063), Chicago, IL 60607 (United States); Shakeri-Zadeh, Ali [Department of Medical Physics, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2010-11-18

    We report a comparative study of synthesis, characteristics and in vitro tests of two folate-conjugated gold nanoparticles (AuNP) differing in linkers and AuNP sizes for selective targeting of folate-receptor positive cancerous cells. The linkers chosen were 4-aminothiophenol (4Atp) and 6-mercapto-1-hexanol (MH) with nanoconjugate products named Folate-4Atp-AuNP and Folate-MH-AuNP. We report the folate-receptor tissue distribution and its endocytosis for targeted nanotechnology. Comparison of the two nanoconjugates’ syntheses and characterization is also reported, including materials and methods of synthesis, UV-visible absorption spectroscopic measurements, Fourier Transform Infra Red (FTIR) measurements, Transmission electron microscopy (TEM) images and size distributions, X-ray diffraction data, elemental analyses and chemical stability comparison. In addition to the analytical characterization of the nanoconjugates, the cell lethality was measured in HeLa (high level of folate receptor expression) and MCF-7 (low level of folate receptor expression) cells. The nanoconjugates themselves, as well as the intense pulsed light (IPL) were not harmful to cell viability. However, upon stimulation of the folate targeted nanoconjugates with the IPL, ~98% cell killing was found in HeLa cells and only ~9% in MCF-7 cells after four hours incubation with the nanoconjugate. This demonstrates that folate targeting is effective in selecting for specific cell populations. Considering the various comparisons made, we conclude that Folate-4Atp-AuNP is superior to Folate-MH-AuNP for cancer therapy.

  20. Design and synthesis of a stable oxidized phospholipid mimic with specific binding recognition for macrophage scavenger receptors

    DEFF Research Database (Denmark)

    Turner, William W; Hartvigsen, Karsten; Boullier, Agnes;

    2012-01-01

    Macrophage scavenger receptors appear to play a major role in the clearance of oxidized phospholipid (OxPL) products. Discrete peptide-phospholipid conjugates with the phosphatidylcholine headgroup have been shown to exhibit binding affinity for these receptors. We report the preparation of a wat...

  1. Human glutathione S-transferase-mediated glutathione conjugation of curcumin and efflux of these conjugates in caco-2 cells

    NARCIS (Netherlands)

    Usta, M.; Wortelboer, H.M.; Vervoort, J.; Boersma, M.G.; Rietjens, I.M.C.M.; Bladeren, P.J. van; Cnubben, N.H.P.

    2007-01-01

    Curcumin, an α,β-unsaturated carbonyl compound, reacts with glutathione, leading to the formation of two monoglutathionyl curcumin conjugates. In the present study, the structures of both glutathione conjugates of curcumin were identified by LC-MS and one- and two-dimensional 1H NMR analysis, and th

  2. Are conjugated linolenic acid isomers an alternative to conjugated linoleic acid isomers in obesity prevention?

    Science.gov (United States)

    Miranda, Jonatan; Arias, Noemi; Fernández-Quintela, Alfredo; del Puy Portillo, María

    2014-04-01

    Despite its benefits, conjugated linoleic acid (CLA) may cause side effects after long-term administration. Because of this and the controversial efficacy of CLA in humans, alternative biomolecules that may be used as functional ingredients have been studied in recent years. Thus, conjugated linolenic acid (CLNA) has been reported to be a potential anti-obesity molecule which may have additional positive effects related to obesity. According to the results reported in obesity, CLNA needs to be given at higher doses than CLA to be effective. However, because of the few studies conducted so far, it is still difficult to reach clear conclusions about the potential use of these CLNAs in obesity and its related changes (insulin resistance, dyslipidemia, or inflammation). Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  3. Dye linked conjugated homopolymers: using conjugated polymer electroluminescence to optically pump porphyrin-dye emission

    DEFF Research Database (Denmark)

    Nielsen, K.T.; Spanggaard, H.; Krebs, Frederik C

    2004-01-01

    . Electroluminescent devices of the homopolymer itself and of the zinc-porphyrin containing polymer were prepared and the nature of the electroluminescence was characterized. The homopolymer segments were found to optically pump the emission of the zinc-porphyrin dye moities. The homopolymer exhibits blue......Zinc-porphyrin dye molecules were incorporated into the backbone of a conjugated polymer material by a method, which allowed for the incorporation of only one zinc-porphyrin dye molecule into the backbone of each conjugated polymer molecule. The electronic properties of the homopolymer were......-green emission and the zinc-porphyrin linked homopolymers emit near-infrared/infrared light. This was demonstrated to be due to electroluminescence pumping of the zinc-porphyrin moieties that were covalently linked to homopolymer material. When only one zinc-porphyrin dye was incorporated into the backbone...

  4. Conjugated polymers with pyrrole as the conjugated bridge: synthesis, characterization, and two-photon absorption properties.

    Science.gov (United States)

    Li, Qianqian; Zhong, Cheng; Huang, Jing; Huang, Zhenli; Pei, Zhiguo; Liu, Jun; Qin, Jingui; Li, Zhen

    2011-07-14

    The synthesis, one- and two-photon absorption (2PA) and emission properties of two novel pyrrole-based conjugated polymers (P1 and P2) are reported. They emitted strong yellow-green and orange fluorescence with fluorescent quantum yields (Φ) of 46 and 33%, respectively. Their maximal 2PA cross sections (δ) measured by the two-photon-induced fluorescence method using femtosecond laser pulses in THF were 2392 and 1938 GM per repeating unit, respectively, indicating that the 2PA chromophores consisting of the triphenylamine with nonplanar structure as the donor and electron-rich pyrrole as the conjugated bridge could be the effective repeating units to enhance the δ values.

  5. Charge Injection and Transport in Conjugated Polymers.

    Science.gov (United States)

    Malliaras, George

    2007-03-01

    We will overview the state-of-the-art in our understanding of charge injection and transport in conjugated polymers. We start by discussing the identifying characteristics of this class of materials, especially in relation with their structure and morphology. We follow by reviewing the advantages and limitations of experimental techniques that are used to probe charge transport. We then embark on a discussion of the fundamentals of charge transport in organics. We follow a didactic approach, where we start from transport in crystalline semiconductors and gradually introduce corrections for space charge effects, for the influence of disorder on mobility, for high charge densities, and for electric field-dependent charge densities. We compare with experimental data from polyfluorenes. We then shift our attention to charge injection. We review some of the recent theories and compared their predictions to experimental data, again from polyfluorenes. We close by proposing directions for future work.

  6. Monotone operators and "bigger conjugate" functions

    CERN Document Server

    Bauschke, Heinz H; Wang, Xianfu; Yao, Liangjin

    2011-01-01

    We study a question posed by Stephen Simons in his 2008 monograph involving "bigger conjugate" (BC) functions and the partial infimal convolution. As Simons demonstrated in his monograph, these function have been crucial to the understanding and advancement of the state-of-the-art of harder problems in monotone operator theory, especially the sum problem. In this paper, we provide some tools for further analysis of BC--functions which allow us to answer Simons' problem in the negative. We are also able to refute a similar but much harder conjecture which would have generalized a classical result of Br\\'ezis, Crandall and Pazy. Our work also reinforces the importance of understanding unbounded skew linear relations to construct monotone operators with unexpected properties.

  7. Conjugated Linoleic Acid and Importance to Health

    Directory of Open Access Journals (Sweden)

    Canan Asal Ulus

    2017-01-01

    Full Text Available The development in science  technology and the researches made in the health field showed that nutrition increases the effectiveness of medical treatment as well as maintaining the human health and singularly effective in the treatment of certain diseases. In recent years, the importance of nutritional elements called ‘Functional foods’ has increased. Functional foods provide physiological benefits and can reduce the risk of chronic diseases beyond their nutritional benefits. One of these functional compounds is conjugated linoleic acid (CLA isomers which have significant effects on human health and previously have been demonstrated in the researches carried out on people and animals. CLA’s attracted more attention after detection of its body fat accumulation reducing, antidiabetic, immune system enhancing, arteriosclerosis reducing, bone mineralization increasing effects.

  8. Identification of excited states in conjugated polymers

    CERN Document Server

    Hartwell, L J

    2003-01-01

    This thesis reports quasi steady state photoinduced absorption measurements from three conjugated polymers: polypyridine (PPy), polyfluorene (PFO) and the emeraldine base (EB) form of polyaniline. The aim of these experiments was to determine the nature of the photoexcited states existing in these materials in the millisecond time domain, as this has important consequences for the operation of real devices manufactured using these materials. The results from the photoinduced absorption experiments are closely compared with published results from pulse radiolysis experiments. In all cases there is very good correspondence between the two data sets, which has enabled the photoexcited states to be assigned with a high degree of confidence. Quasi steady-state photoinduced absorption involves the measurement of the change in absorption of a material in response to optical excitation with a laser beam. The changes in absorption are small, so a instrument was developed and optimised for each different sample. Lock-i...

  9. Spiropyran main-chain conjugated polymers.

    Science.gov (United States)

    Sommer, Michael; Komber, Hartmut

    2013-01-11

    The first main-chain conjugated copolymers based on alternating spiropyran (SP) and 9,9-dioctylfluorene (F8) units synthesized via Suzuki polycondensation (SPC) are presented. The reaction conditions of SPC are optimized to obtain materials of type P(para-SP-F8) with appreciably high molecular weights up to M(w) ≈ 100 kg mol(-1). (13)C NMR is used to identify the random orientation of the non-symmetric SP unit in P(p-SP-F8). Ultrasound-induced isomerization of P(p-SP-F8) to the corresponding merocyanine form P(p-MC-F8) yields a deep-red solution. This isomerization reaction is followed by (1)H NMR in solution using sonication, whereby the color increasingly changes to deep red. The possibility to incorporate multiple SP units into main-chain polymers significantly broadens existing SP-based polymeric architectures.

  10. Nonlinear optical response in doped conjugated polymers

    CERN Document Server

    Harigaya, K

    1995-01-01

    Exciton effects on conjugated polymers are investigated in soliton lattice states. We use the Su-Schrieffer-Heeger model with long-range Coulomb interactions. The Hartree-Fock (HF) approximation and the single-excitation configuration- interaction (single-CI) method are used to obtain optical absorption spectra. The third-harmonic generation (THG) at off-resonant frequencies is calculated as functions of the soliton concentration and the chain length of the polymer. The magnitude of the THG at the 10 percent doping increases by the factor about 10^2 from that of the neutral system. This is owing to the accumulation of the oscillator strengths at the lowest exciton with increasing the soliton concentration. The increase by the order two is common for several choices of Coulomb interaction strengths.

  11. Conjugated Linoleic Acid (CLA-An Overview

    Directory of Open Access Journals (Sweden)

    D J Crumb

    2011-09-01

    Full Text Available Summary: Conjugated linoleic acid (CLA is a group of octadecadienoic acids that are naturally present in the highest concentrations in foods originating in ruminant animals, and dairy products such as milk. Especially large numbers of CLA polymers have been detected in beef, lamb and milk fat. Results from many in vitro and animal studies, though conflicting, have suggested that CLA supplementation may have beneficial effect on obesity, weight management, cancer, diabetes and atherosclerosis. This article provides a brief overview on the functionality, safety and toxicity of CLA as described in literature. .   Industrial Relevance: CLA is a functional food and dietary supplement ingredient with potential benefits against a number of metabolic chronic diseases. However, the mechanism of action and its toxicological effects are not very well understood. These factors may play an important role in the effectiveness as CLA as a viable functional dietary bioactive compound.

  12. Coexistence of Self-pumped Phase Conjugation and Mutual-pumped Phase Conjugation in Ce∶BaTiO3

    Institute of Scientific and Technical Information of China (English)

    SHE Weilong; Lee Wing-Kee

    2000-01-01

    Self-pumped phase conjugation(SPPC) and mutual-pumped phase conjugation (MPPC) have been found to coexist in Ce∶BaTiO3 by using two coherent beams of 514.5nm wavelength from an argon ion laser. Both phase conjugations are of the stimulated backscattering and four-wave mixing type. For 7/6 incident power ratio and 26 mW total incident power,he shortest phase conjugate mirror formation time is 10s . Phase conjugate reflectivity of one the beams can reach 70%,hich is ~20% higher than the SPPC reflectivity using only one beam. When the total incident power is increased to 40 mW and the incident power ratio remains constant,a maximum phase conjugatate reflectivity of as much as 88% is obtained.

  13. Native mass spectrometry and ion mobility characterization of trastuzumab emtansine, a lysine-linked antibody drug conjugate

    Science.gov (United States)

    Marcoux, Julien; Champion, Thierry; Colas, Olivier; Wagner-Rousset, Elsa; Corvaïa, Nathalie; Van Dorsselaer, Alain; Beck, Alain; Cianférani, Sarah

    2015-01-01

    Antibody–drug conjugates (ADCs) are biochemotherapeutics consisting of a cytotoxic chemical drug linked covalently to a monoclonal antibody. Two main classes of ADCs, namely cysteine and lysine conjugates, are currently available on the market or involved in clinical trials. The complex structure and heterogeneity of ADCs makes their biophysical characterization challenging. For cysteine conjugates, hydrophobic interaction chromatography is the gold standard technique for studying drug distribution, the naked antibody content, and the average drug to antibody ratio (DAR). For lysine ADC conjugates on the other hand, which are not amenable to hydrophobic interaction chromatography because of their higher heterogeneity, denaturing mass spectrometry (MS) and UV/Vis spectroscopy are the most powerful approaches. We report here the use of native MS and ion mobility (IM-MS) for the characterization of trastuzumab emtansine (T-DM1, Kadcyla®). This lysine conjugate is currently being considered for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and combines the anti-HER2 antibody trastuzumab (Herceptin®), with the cytotoxic microtubule-inhibiting maytansine derivative, DM1. We show that native MS combined with high-resolution measurements and/or charge reduction is beneficial in terms of the accurate values it provides of the average DAR and the drug load profiles. The use of spectral deconvolution is discussed in detail. We report furthermore the use of native IM-MS to directly determine DAR distribution profiles and average DAR values, as well as a molecular modeling investigation of positional isomers in T-DM1. PMID:25694334

  14. CD33 monoclonal antibody conjugated Au cluster nano-bioprobe for targeted flow-cytometric detection of acute myeloid leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Retnakumari, Archana; Jayasimhan, Jasusri; Chandran, Parwathy; Menon, Deepthy; Nair, Shantikumar; Mony, Ullas; Koyakutty, Manzoor, E-mail: manzoork@aims.amrita.edu, E-mail: ullasmony@aims.amrita.edu [Amrita Centre for Nanoscience and Molecular Medicine, Amrita Institute of Medical Science, Cochin 682 041 (India)

    2011-07-15

    Protein stabilized gold nanoclusters (Au-NCs) are biocompatible, near-infrared (NIR) emitting nanosystems having a wide range of biomedical applications. Here, we report the development of a Au-NC based targeted fluorescent nano-bioprobe for the flow-cytometric detection of acute myeloid leukaemia (AML) cells. Au-NCs with {approx} 25-28 atoms showing bright red-NIR fluorescence (600-750 nm) and average size of {approx} 0.8 nm were prepared by bovine serum albumin assisted reduction-cum-stabilization in aqueous phase. The protein protected clusters were conjugated with monoclonal antibody against CD33 myeloid antigen, which is overexpressed in {approx} 99.2% of the primitive population of AML cells, as confirmed by immunophenotyping using flow cytometry. Au-NC-CD33 conjugates having average size of {approx} 12 nm retained bright fluorescence over an extended duration of {approx} a year, as the albumin protein protects Au-NCs against degradation. Nanotoxicity studies revealed excellent biocompatibility of Au-NC conjugates, as they showed no adverse effect on the cell viability and inflammatory response. Target specificity of the conjugates for detecting CD33 expressing AML cells (KG1a) in flow cytometry showed specific staining of {approx} 95.4% of leukaemia cells within 1-2 h compared to a non-specific uptake of {approx} 8.2% in human peripheral blood cells (PBMCs) which are CD33{sup low}. The confocal imaging also demonstrated the targeted uptake of CD33 conjugated Au-NCs by leukaemia cells, thus confirming the flow cytometry results. This study demonstrates that novel nano-bioprobes can be developed using protein protected fluorescent nanoclusters of Au for the molecular receptor targeted flow cytometry based detection and imaging of cancer cells.

  15. A novel 2,6-diisopropylphenyl-docosahexaenoamide conjugate induces apoptosis in T cell acute lymphoblastic leukemia cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Altenburg, Jeffrey D.; Harvey, Kevin A.; McCray, Sharon; Xu, Zhidong [Cellular Biochemistry Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN (United States); Siddiqui, Rafat A., E-mail: rsiddiqu@iuhealth.org [Cellular Biochemistry Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN (United States); Department of Biology, Indiana University-Purdue University, Indianapolis, IN (United States); Department of Medicine, Indiana University School of Medicine, Indianapolis, IN (United States)

    2011-07-29

    Highlights: {yields} 2,6-Diisopropylphenyl-docosahexaenoamide conjugates (DIP-DHA) inhibits the proliferation of T-cell leukemic cell lines. {yields} DIP-DHA resulted in increased activation of caspase-3, and caspase-7. {yields} DIP-DHA significantly downregulated CXCR4 surface expression. -- Abstract: We have previously characterized the effects of 2,6-diisopropylphenyl-docosahexaenoamide (DIP-DHA) conjugates and their analogs on the proliferation and progression of breast cancer cell lines. For this study, we investigated the effects of the DIP-DHA conjugate on 2 representative T cell acute lymphoblastic leukemia (T-ALL) cell lines: CEM and Jurkat. Treatment of both cell lines with DIP-DHA resulted in significantly greater inhibition of proliferation and induction of apoptosis than that of parent compounds, 2,6-diisopropylphenol (DIP) or docosahexaenoate (DHA). Treatment of the cells with DIP-DHA resulted in increased activation of caspase-3, and caspase-7. Furthermore, induction of apoptosis in both cell lines was reversed in the presence of a caspase family inhibitor. Treatment with DIP-DHA reduced mitochondrial membrane potential. These observations suggest that the effects are driven by intrinsic apoptotic pathways. DIP-DHA treatment also downregulated surface CXCR4 expression, an important chemokine receptor involved in cancer metastasis that is highly expressed in both CEM and Jurkat cells. In conclusion, our data suggest that the DIP-DHA conjugate exhibits significantly more potent effects on CEM and Jurkat cells than that of DIP or DHA alone. These conjugates have potential use for treatment of patients with T cell acute lymphoblastic leukemia.

  16. IRDye78 Conjugates for Near-Infrared Fluorescence Imaging

    Directory of Open Access Journals (Sweden)

    Atif Zaheer

    2002-10-01

    Full Text Available The detection of human malignancies by near-infrared (NIR fluorescence will require the conjugation of cancer-specific ligands to NIR fluorophores that have optimal photoproperties and pharmacokinetics. IRDye78, a tetra-sulfonated heptamethine indocyanine NIR fluorophore, meets most of the criteria for an in vivo imaging agent, and is available as an N-hydroxysuccinimide ester for conjugation to low-molecular-weight ligands. However, IRDye78 has a high charge-to-mass ratio, complicating purification of conjugates. It also has a potentially labile linkage between fluorophore and ligand. We have developed an ion-pairing purification strategy for IRDye78 that can be performed with a standard C18 column under neutral conditions, thus preserving the stability of fluorophore, ligand, and conjugate. By employing parallel evaporative light scatter and absorbance detectors, all reactants and products are identified, and conjugate purity is maximized. We describe reversible and irreversible conversions of IRDye78 that can occur during sample purification, and describe methods for preserving conjugate stability. Using seven ligands, spanning several classes of small molecules and peptides (neutral, charged, and/or hydrophobic, we illustrate the robustness of these methods, and confirm that IRDye78 conjugates so purified retain bioactivity and permit NIR fluorescence imaging of specific targets.

  17. Nanostructured conjugated polymers in chemical sensors: synthesis, properties and applications.

    Science.gov (United States)

    Correa, D S; Medeiros, E S; Oliveira, J E; Paterno, L G; Mattoso, Luiz C

    2014-09-01

    Conjugated polymers are organic materials endowed with a π-electron conjugation along the polymer backbone that present appealing electrical and optical properties for technological applications. By using conjugated polymeric materials in the nanoscale, such properties can be further enhanced. In addition, the use of nanostructured materials makes possible miniaturize devices at the micro/nano scale. The applications of conjugated nanostructured polymers include sensors, actuators, flexible displays, discrete electronic devices, and smart fabric, to name a few. In particular, the use of conjugated polymers in chemical and biological sensors is made feasible owning to their sensitivity to the physicochemical conditions of its surrounding environment, such as chemical composition, pH, dielectric constant, humidity or even temperature. Subtle changes in these conditions bring about variations on the electrical (resistivity and capacitance), optical (absorptivity, luminescence, etc.), and mechanical properties of the conjugated polymer, which can be precisely measured by different experimental methods and ultimately associated with a specific analyte and its concentration. The present review article highlights the main features of conjugated polymers that make them suitable for chemical sensors. An especial emphasis is given to nanostructured sensors systems, which present high sensitivity and selectivity, and find application in beverage and food quality control, pharmaceutical industries, medical diagnosis, environmental monitoring, and homeland security, and other applications as discussed throughout this review.

  18. Synthesis and antimicrobial activity of gold nanoparticle conjugates with cefotaxime

    Science.gov (United States)

    Titanova, Elena O.; Burygin, Gennady L.

    2016-04-01

    Gold nanoparticles (GNPs) have attracted significant interest as a novel platform for various applications to nanobiotechnology and biomedicine. The conjugates of GNPs with antibiotics and antibodies were also used for selective photothermal killing of protozoa and bacteria. Also the conjugates of some antibiotics with GNPs decreased the number of bacterial growing cells. In this work was made the procedure optimization for conjugation of cefotaxime (a third-generation cephalosporin antibiotic) with GNPs (15 nm) and we examined the antimicrobial properties of this conjugate to bacteria culture of E. coli K-12. Addition of cefotaxime solution to colloidal gold does not change their color and extinction spectrum. For physiologically active concentration of cefotaxime (3 μg/mL), it was shown that the optimum pH for the conjugation was more than 9.5. A partial aggregation of the GNPs in saline medium was observed at pH 6.5-7.5. The optimum concentration of K2CO3 for conjugation cefotaxime with GNPs-15 was 5 mM. The optimum concentration of cefotaxime was at 0.36 μg/mL. We found the inhibition of the growth of E. coli K12 upon application cefotaxime-GNP conjugates.

  19. Orthogonal assembly of a designed ankyrin repeat protein-cytotoxin conjugate with a clickable serum albumin module for half-life extension.

    Science.gov (United States)

    Simon, Manuel; Frey, Raphael; Zangemeister-Wittke, Uwe; Plückthun, Andreas

    2013-11-20

    The generation of drug conjugates for safe and effective tumor targeting requires binding proteins tolerant to functionalization by rational engineering. Here, we show that Designed Ankyrin Repeat Proteins (DARPins), a novel class of binding proteins not derived from antibodies, can be used as building blocks for facile orthogonal assembly of bioconjugates for tumor targeting with tailored properties. DARPin Ec1, which targets the Epithelial Cell Adhesion Molecule (EpCAM), was genetically modified with a C-terminal cysteine for conjugation of the small molecule cytotoxin monomethylauristatin F (MMAF). In addition, it was N-terminally functionalized by metabolic introduction of the non-natural amino acid azidohomoalanine to enable linkage of site-specifically dibenzocyclooctyne-modified mouse serum albumin (MSA) for half-life extension using Cu(I)-free click chemistry. The conjugate MSA-Ec1-MMAF was assembled to obtain high yields of a pure and stable drug conjugate as confirmed by various analytical methods and in functional assays. The orthogonality of the assembly led to a defined reaction product and preserved the functional properties of all modules, including EpCAM-specific binding and internalization, FcRn binding mediated by MSA, and cytotoxic potency. Linkage of MMAF to the DARPin increased receptor-specific uptake of the drug while decreasing nonspecific uptake, and further coupling of the conjugate to MSA enhanced this effect. In mice, albumin conjugation increased the serum half-life from 11 min to 17.4 h, resulting in a more than 22-fold increase in the area-under-the-curve (AUC). Our data demonstrate the promise of the DARPin format for facile modular assembly of drug conjugates with improved pharmacokinetic performance for tumor targeting.

  20. Conjugation efficiency depends on intra and intercellular interactions between distinct plasmids: Plasmids promote the immigration of other plasmids but repress co-colonizing plasmids.

    Science.gov (United States)

    Gama, João Alves; Zilhão, Rita; Dionisio, Francisco

    2017-08-24

    Conjugative plasmids encode the genes responsible for the synthesis of conjugative pili and plasmid transfer. Expression of the conjugative machinery (including conjugative pili) may be costly to bacteria, not only due to the energetic/metabolic cost associated with their expression but also because they serve as receptors for certain viruses. Consequently, the presence of two plasmids in the same cell may be disadvantageous to each plasmid, because they may impose a higher fitness cost on the host. Therefore, plasmids may encode mechanisms to cope with co-resident plasmids. Moreover, it is possible that the transfer rate of a plasmid is affected by the presence of a distinct plasmid in the recipient cell. In this work, we measured transfer rates of twelve natural plasmids belonging to seven incompatibility groups in three situations, namely when: (i) donor cells contain a plasmid and recipient cells are plasmid-free; (ii) donor cells contain two unrelated plasmids and recipient cells are plasmid-free; and (iii) half of the cells contain a given plasmid and the other half contain another, unrelated, plasmid. In the third situation, recipient cells of a plasmid are the donor cells of the other plasmid. We show that there are more negative interactions (reduction of a plasmid's conjugative efficiency) between plasmids if they reside in the same cell than if they reside in different cells. However, if plasmids interacted intercellularly, the transfer rate of one of the plasmids was often higher (when the unrelated conjugative plasmid was present in the recipient cell) than if the recipient cell was plasmid-free - a positive effect. Experimental data retrieved from the study of mutant plasmids not expressing conjugative pili on the cell surface suggest that positive effects result from a higher efficiency of mating pair formation. Overall, our results suggest that negative interactions are significantly more frequent when plasmids occupy the same cell. Such

  1. p-Hydroxy benzoic acid-conjugated dendrimer nanotherapeutics as potential carriers for targeted drug delivery to brain: an in vitro and in vivo evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Swami, Rajan; Singh, Indu [National Institute of Pharmaceutical Education & Research (NIPER), Department of Pharmaceutics (India); Kulhari, Hitesh [CSIR-Indian Institute of Chemical Technology, Medicinal Chemistry & Pharmacology Division (India); Jeengar, Manish Kumar [National Institute of Pharmaceutical Education & Research (NIPER), Departmentof Pharmacology (India); Khan, Wahid, E-mail: wahid@niperhyd.ac.in; Sistla, Ramakrishna, E-mail: sistla@iict.res.in, E-mail: rksistla@yahoo.com [National Institute of Pharmaceutical Education & Research (NIPER), Department of Pharmaceutics (India)

    2015-06-15

    Dendrimers which are discrete nanostructures/nanoparticles are emerging as promising candidates for many nanomedicine applications. Ligand-conjugated dendrimer facilitate the delivery of therapeutics in a targeted manner. Small molecules such as p-hydroxyl benzoic acid (pHBA) were found to have high affinity for sigma receptors which are prominent in most parts of central nervous system and tumors. The aim of this study was to synthesize pHBA-dendrimer conjugates as colloidal carrier for site-specific delivery of practically water insoluble drug, docetaxel (DTX) to brain tumors and to determine its targeting efficiency. pHBA, a small molecule ligand was coupled to the surface amine groups of generation 4-PAMAM dendrimer via a carbodiimide reaction and loaded with DTX. The conjugation was confirmed by {sup 1}HNMR and FT-IR spectroscopy. In vitro release of drug from DTX-loaded pHBA-conjugated dendrimer was found to be less as compared to unconjugated dendrimers. The prepared drug delivery system exhibited good physico-chemical stability and decrease in hemolytic toxicity. Cell viability and cell uptake studies were performed against U87MG human glioblastoma cells and formulations exerted considerable anticancer effect than plain drug. Conjugation of dendrimer with pHBA significantly enhanced the brain uptake of DTX which was shown by the recovery of a higher percentage of the dose from the brain following administration of pHBA-conjugated dendrimers compared with unconjugated dendrimer or formulation in clinical use (Taxotere{sup ®}). Therefore, pHBA conjugated dendrimers could be an efficient delivery vehicle for the targeting of anticancer drugs to brain tumors.

  2. Conjugation vs hyperconjugation in molecular structure of acrolein

    Science.gov (United States)

    Shishkina, Svitlana V.; Slabko, Anzhelika I.; Shishkin, Oleg V.

    2013-01-01

    Analysis of geometric parameters of butadiene and acrolein reveals the contradiction between the Csp2-Csp2 bond length in acrolein and classical concept of conjugation degree in the polarized molecules. In this Letter the reasons of this contradiction have been investigated. It is concluded that the Csp2-Csp2 bond length in acrolein is determined by influence of the bonding for it π-π conjugation and antibonding n → σ∗ hyperconjugation between the oxygen lone pair and the antibonding orbital of the single bond. It was shown also this bond length depends on the difference in energy of conjugative and hyperconjugative interactions.

  3. CONJUGATED POLYMERS AND POLYELECTROLYTES IN SOLAR PHOTOCONVERSION, Final Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    Schanze, Kirk S [University of Florida

    2014-08-05

    This DOE-supported program investigated the fundamental properties of conjugated polyelectrolytes, with emphasis placed on studies of excited state energy transport, self-assembly into conjugated polyelectroyte (CPE) based films and colloids, and exciton transport and charge injection in CPE films constructed atop wide bandgap semiconductors. In the most recent grant period we have also extended efforts to examine the properties of low-bandgap donor-acceptor conjugated polyelectrolytes that feature strong visible light absorption and the ability to adsorb to metal-oxide interfaces.

  4. Vibrational spectroscopy of microhydrated conjugate base anions.

    Science.gov (United States)

    Asmis, Knut R; Neumark, Daniel M

    2012-01-17

    Conjugate-base anions are ubiquitous in aqueous solution. Understanding the hydration of these anions at the molecular level represents a long-standing goal in chemistry. A molecular-level perspective on ion hydration is also important for understanding the surface speciation and reactivity of aerosols, which are a central component of atmospheric and oceanic chemical cycles. In this Account, as a means of studying conjugate-base anions in water, we describe infrared multiple-photon dissociation spectroscopy on clusters in which the sulfate, nitrate, bicarbonate, and suberate anions are hydrated by a known number of water molecules. This spectral technique, used over the range of 550-1800 cm(-1), serves as a structural probe of these clusters. The experiments follow how the solvent network around the conjugate-base anion evolves, one water molecule at a time. We make structural assignments by comparing the experimental infrared spectra to those obtained from electronic structure calculations. Our results show how changes in anion structure, symmetry, and charge state have a profound effect on the structure of the solvent network. Conversely, they indicate how hydration can markedly affect the structure of the anion core in a microhydrated cluster. Some key results include the following. The first few water molecules bind to the anion terminal oxo groups in a bridging fashion, forming two anion-water hydrogen bonds. Each oxo group can form up to three hydrogen bonds; one structural result, for example, is the highly symmetric, fully coordinated SO(4)(2-)(H(2)O)(6) cluster, which only contains bridging water molecules. Adding more water molecules results in the formation of a solvent network comprising water-water hydrogen bonding in addition to hydrogen bonding to the anion. For the nitrate, bicarbonate, and suberate anions, fewer bridging sites are available, namely, three, two, and one (per carboxylate group), respectively. As a result, an earlier onset of water

  5. Conjugated organometallic materials containing tungsten centers

    Science.gov (United States)

    Jones, Marya

    Our group is interested in the optical and electronic properties of organometallic analogues of conjugated organic compounds. Specifically, in this thesis we will discuss the properties of complexes in which W≡C moieties replace C≡C fragments within the framework of oligo(phenyleneethynylenes) and a C4-polyyne. A family of derivatives of the type Ph(C≡CC6H4 )m(L)4W≡C(C6H 4C≡C)nPh (m = 0, 1; n = 0, 1, 2) have been prepared and characterized by X-ray crystallography, electronic-absorption spectroscopy, and electrochemistry. This substitution has allowed us to directly compare the electronic and optical properties of these organometallic complexes with those of their organic analogues. We found that while these systems exhibit redox and spectroscopic properties similar to those of their organic counterparts they also exhibit new characteristics that are due to the incorporation of the metal center. The design of these compounds has also allowed us to address how the position of the metal within the backbone affects the electronic and optical properties of these compounds. We found that the position of the metal is important in controlling the electronic structure of the material, thus suggesting that the properties of these compounds can be further tuned by changing the position of the metal within the conjugated carbon chain. In addition, we have appended sulfur and isocyanide functionalities to oligo(phenyleneethynylene) analogues. A family of compounds of the type Cl(dppe) 2W(≡CC6H4-4-(C≡CC6H 4)m-4'-R) (m = l, 2; R = N≡C, SCH2CH 2Si(CH3)3) have been prepared and characterized by electronic-absorption spectroscopy and electrochemistry. Differences between the sulfur and isocyanide functionalities are examined, along with the effects of extending conjugation along the arylidyne chain. Evidence that the sulfur-containing arylidyne complexes form self-assembled monolayers on Au and Pt electrodes is presented. In addition, the electron-transfer rates for

  6. Generic method for the absolute quantification of glutathione S-conjugates: Application to the conjugates of acetaminophen, clozapine and diclofenac.

    Science.gov (United States)

    den Braver, Michiel W; Vermeulen, Nico P E; Commandeur, Jan N M

    2017-03-01

    Modification of cellular macromolecules by reactive drug metabolites is considered to play an important role in the initiation of tissue injury by many drugs. Detection and identification of reactive intermediates is often performed by analyzing the conjugates formed after trapping by glutathione (GSH). Although sensitivity of modern mass spectrometrical methods is extremely high, absolute quantification of GSH-conjugates is critically dependent on the availability of authentic references. Although (1)H NMR is currently the method of choice for quantification of metabolites formed biosynthetically, its intrinsically low sensitivity can be a limiting factor in quantification of GSH-conjugates which generally are formed at low levels. In the present study, a simple but sensitive and generic method for absolute quantification of GSH-conjugates is presented. The method is based on quantitative alkaline hydrolysis of GSH-conjugates and subsequent quantification of glutamic acid and glycine by HPLC after precolumn derivatization with o-phthaldialdehyde/N-acetylcysteine (OPA/NAC). Because of the lower stability of the glycine OPA/NAC-derivate, quantification of the glutamic acid OPA/NAC-derivate appeared most suitable for quantification of GSH-conjugates. The novel method was used to quantify the concentrations of GSH-conjugates of diclofenac, clozapine and acetaminophen and quantification was consistent with (1)H NMR, but with a more than 100-fold lower detection limit for absolute quantification. Copyright © 2017. Published by Elsevier B.V.

  7. Lipoxin Receptors

    Directory of Open Access Journals (Sweden)

    Mario Romano

    2007-01-01

    Full Text Available Lipoxins (LXs represent a class of arachidonic acid (AA metabolites that carry potent immunoregulatory and anti-inflammatory properties, LXA4 and LXB4 being the main components of this series. LXs are generated by cooperation between 5-lipoxygenase (LO and 12- or 15-LO during cell-cell interactions or by single cell types. LX epimers at carbon 15, the 15-epi-LXs, are formed by aspirin-acetylated cyclooxygenase-2 (COX-2 in cooperation with 5-LO. 15-epi-LXA4 is also termed aspirin-triggered LX (ATL. In vivo studies with stable LX and ATL analogs have established that these eicosanoids possess potent anti-inflammatory activities. A LXA4 receptor has been cloned. It belongs to the family of chemotactic receptors and clusters with formyl peptide receptors on chromosome 19. Therefore, it was initially denominated formyl peptide receptor like 1 (FPRL1. This receptor binds with high affinity and stereoselectivity LXA4 and ATL. It also recognizes a variety of peptides, synthetic, endogenously generated, or disease associated, but with lower affinity compared to LXA4. For this reason, this receptor has been renamed ALX. This review summarizes the current knowledge on ALX expression, signaling, and potential pathophysiological role. The involvement of additional recognition sites in LX bioactions is also discussed.

  8. Biotin-conjugated tumour-targeting photocytotoxic iron(III) complexes.

    Science.gov (United States)

    Saha, Sounik; Majumdar, Ritankar; Hussain, Akhtar; Dighe, Rajan R; Chakravarty, Akhil R

    2013-07-28

    Iron(III) complexes [FeL(B)] (1-4) of a tetradentate phenolate-based ligand (H3L) and biotin-conjugated dipyridophenazine bases (B), viz. 7-aminodipyrido [3,2-a:2',3'-c]-phenazine (dppza in 1), (N-dipyrido[3,2-a:2',3'-c]-phenazino)amidobiotin (dppzNB in 2), dipyrido [3,2-a:2',3'-c]-phenazine-11-carboxylic acid (dppzc in 3) and 2-((2-biotinamido)ethyl) amido-dipyrido[3,2-a:2',3'-c]-phenazine (dppzCB in 4) are prepared, characterized and their interaction with streptavidin and DNA and their photocytotoxicity and cellular uptake in various cells studied. The high-spin iron(III) complexes display Fe(III)/Fe(II) redox couple near -0.7 V versus saturated calomel electrode in dimethyl sulfoxide-0.1 M tetrabutylammonium perchlorate. The complexes show non-specific interaction with DNA as determined from the binding studies. Complexes with appended biotin moiety show similar binding to streptavidin as that of free biotin, suggesting biotin conjugation to dppz does not cause any loss in its binding affinity to streptavidin. The photocytotoxicity of the complexes is tested in HepG2, HeLa and HEK293 cell lines. Complex 2 shows higher photocytotoxicity in HepG2 cells than in HeLa or HEK293, forming reactive oxygen species. This effect is attributed to the presence of overexpressed sodium-dependent multi-vitamin transporters in HepG2 cells. Microscopic studies in HepG2 cells show internalization of the biotin complexes 2 and 4 essentially occurring by receptor-mediated endocytosis, which is similar to that of native biotin and biotin fluorescein isothiocyanate conjugate.

  9. Fluorescent ligand for human progesterone receptor imaging in live cells.

    Science.gov (United States)

    Weinstain, Roy; Kanter, Joan; Friedman, Beth; Ellies, Lesley G; Baker, Michael E; Tsien, Roger Y

    2013-05-15

    We employed molecular modeling to design and then synthesize fluorescent ligands for the human progesterone receptor. Boron dipyrromethene (BODIPY) or tetramethylrhodamine were conjugated to the progesterone receptor antagonist RU486 (Mifepristone) through an extended hydrophilic linker. The fluorescent ligands demonstrated comparable bioactivity to the parent antagonist in live cells and triggered nuclear translocation of the receptor in a specific manner. The BODIPY labeled ligand was applied to investigate the dependency of progesterone receptor nuclear translocation on partner proteins and to show that functional heat shock protein 90 but not immunophilin FKBP52 activity is essential. A tissue distribution study indicated that the fluorescent ligand preferentially accumulates in tissues that express high levels of the receptor in vivo. The design and properties of the BODIPY-labeled RU486 make it a potential candidate for in vivo imaging of PR by positron emission tomography through incorporation of (18)F into the BODIPY core.

  10. Synthesis and Characterization of Sodium Alginate Conjugate and Study of Effect of Conjugation on Drug Release from Matrix Tablet

    OpenAIRE

    Satheeshababu, B. K.; Mohamed, I.

    2015-01-01

    The aim of the present research work to study the effect of conjugation of the polymer on drug release from the matrix tablets. Sodium alginate L-cysteine conjugate was achieved by covalent attachment of thiol group of L-cysteine with the primary amino group of sodium alginate through the amide bonds formed by primary amino groups of the sodium alginate and the carboxylic acid group of L-cysteine. The synthesised sodium alginate L-cysteine conjugate was characterised by determining of charrin...

  11. Development of Viral Capsid DNA Aptamer Conjugates as Cell-Targeted Delivery Vehicles

    Science.gov (United States)

    Tong, Gary Jen-Wei

    cell-targeting delivery vehicles. These agents were generated by selectively functionalizing the interior and exterior surfaces of MS2 with functional molecules and DNA aptamers, respectively, using orthogonal bioconjugation reactions. Interior surface modification was achieved through the incorporation of a uniquely-reactive cysteine residue, while exterior modification occurred via the introduction of the non-natural amino acid p-aminophenylalanine. MS2 capsids possessing interior fluorophores and exterior DNA aptamers targeted to a Jurkat T cell surface receptor were synthesized using this strategy. In cell-binding experiments, these dual-surface modified capsids were shown to bind target cells in an aptamer-dependent manner. In addition, colocalization experiments using confocal microscopy elucidated their cellular internalization pathway. Following validation of the cell-targeting capabilities of aptamer-MS2 conjugates, a multivalent photodynamic agent was developed for targeted photodynamic therapy. This agent was synthesized by installing singlet oxygen-generating porphyrins on the interior of MS2 capsids possessing DNA aptamers on the exterior. Upon illumination with 415 nm light, these dual-modified capsids were shown to generate cytotoxic singlet oxygen. In cell experiments, these agents were shown to selectively kill Jurkat cells in a heterogeneous cell mixture.

  12. Endocytosis of Receptor Tyrosine Kinases

    Science.gov (United States)

    Goh, Lai Kuan

    2013-01-01

    Endocytosis is the major regulator of signaling from receptor tyrosine kinases (RTKs). The canonical model of RTK endocytosis involves rapid internalization of an RTK activated by ligand binding at the cell surface and subsequent sorting of internalized ligand-RTK complexes to lysosomes for degradation. Activation of the intrinsic tyrosine kinase activity of RTKs results in autophosphorylation, which is mechanistically coupled to the recruitment of adaptor proteins and conjugation of ubiquitin to RTKs. Ubiquitination serves to mediate interactions of RTKs with sorting machineries both at the cell surface and on endosomes. The pathways and kinetics of RTK endocytic trafficking, molecular mechanisms underlying sorting processes, and examples of deviations from the standard trafficking itinerary in the RTK family are discussed in this work. PMID:23637288

  13. Matrix summability of the conjugate deries of derived Fourier series

    Directory of Open Access Journals (Sweden)

    Shyam Lal

    2002-03-01

    Full Text Available In this paper, a new theorem on matrix summability of the conjugate series of a derived Fourier series is proved, which improves and generalizes all the previous known results in this line of work.

  14. Phase conjugation of gap solitons: A numerical study

    Indian Academy of Sciences (India)

    V S C Manga Rao; S Dutta Gupta

    2003-09-01

    We study the effect of a nearby phase-conjugate mirror (PCM) on the gap soliton of a Kerr non-linear periodic structure. We show that phase conjugation of the gap soliton (in the sense of replication of the amplitude profile in the reverse direction) is possible under the condition of PCM reflectivity approaching unity. This is in contrast with the results for linear structures, where the wave profiles can be conjugated for arbitrary values of the PCM reflectivity. The sensitivity of the conjugation of the gap solitons to PCM reflectivity is ascribed to the fine balance of non-linearity with dispersion, necessary for their existence.

  15. Conjugate heat transfer with the entropic lattice Boltzmann method.

    Science.gov (United States)

    Pareschi, G; Frapolli, N; Chikatamarla, S S; Karlin, I V

    2016-07-01

    A conjugate heat-transfer model is presented based on the two-population entropic lattice Boltzmann method. The present approach relies on the extension of Grad's boundary conditions to the two-population model for thermal flows, as well as on the appropriate exact conjugate heat-transfer condition imposed at the fluid-solid interface. The simplicity and efficiency of the lattice Boltzmann method (LBM), and in particular of the entropic multirelaxation LBM, are retained in the present approach, thus enabling simulations of turbulent high Reynolds number flows and complex wall boundaries. The model is validated by means of two-dimensional parametric studies of various setups, including pure solid conduction, conjugate heat transfer with a backward-facing step flow, and conjugate heat transfer with the flow past a circular heated cylinder. Further validations are performed in three dimensions for the case of a turbulent flow around a heated mounted cube.

  16. BSA-boronic acid conjugate as lectin mimetics.

    Science.gov (United States)

    Narla, Satya Nandana; Pinnamaneni, Poornima; Nie, Huan; Li, Yu; Sun, Xue-Long

    2014-01-10

    We report bovine serum albumin (BSA)-boronic acid (BA) conjugates as lectin mimetics and their glyco-capturing capacity. The BSA-BA conjugates were synthesized by amidation of carboxylic acid groups in BSA with aminophenyl boronic acid in the presence of EDC, and were characterized by Alizarin Red S (ARS) assay and SDS-PAGE gel. The BSA-BA conjugates were immobilized onto maleimide-functionalized silica beads and their sugar capturing capacity and specificity were confirmed by ARS displacement assay. Further, surface plasmon resonance (SPR) analysis of the glyco-capturing activity of the BSA-BA conjugates was conducted by immobilizing BSA-BA onto SPR gold chip. Overall, we demonstrated a BSA-BA-based lectin mimetics for glyco-capturing applications. These lectin mimetics are expected to provide an important tool for glycomics and biosensor research and applications.

  17. Fullerene-biomolecule conjugates and their biomedicinal applications.

    Science.gov (United States)

    Yang, Xinlin; Ebrahimi, Ali; Li, Jie; Cui, Quanjun

    2014-01-01

    Fullerenes are among the strongest antioxidants and are characterized as "radical sponges." The research on biomedicinal applications of fullerenes has achieved significant progress since the landmark publication by Friedman et al in 1993. Fullerene-biomolecule conjugates have become an important area of research during the past 2 decades. By a thorough literature search, we attempt to update the information about the synthesis of different types of fullerene-biomolecule conjugates, including fullerene-containing amino acids and peptides, oligonucleotides, sugars, and esters. Moreover, we also discuss in this review recently reported data on the biological and pharmaceutical utilities of these compounds and some other fullerene derivatives of biomedical importance. While within the fullerene-biomolecule conjugates, in which fullerene may act as both an antioxidant and a carrier, specific targeting biomolecules conjugated to fullerene will undoubtedly strengthen the delivery of functional fullerenes to sites of clinical interest.

  18. Synthesis and characterization of polyamidoamine conjugates of neridronic acid

    CSIR Research Space (South Africa)

    Aderibigbe, BA

    2015-10-01

    Full Text Available of water and it was performed at room temperature thereby making the reaction environmentally friendly and economically viable. These conjugates are potential prodrugs and they were characterized by nuclear magnetic resonance spectroscopy (NMR), Fourier...

  19. Plasmid Conjugation in E. coli and Drug Resistance

    African Journals Online (AJOL)

    Prof. Ogunji

    respiratory infections etc) or prescribing the 'newest' antibiotics in the market when older “brands” may ..... influence an increase in mortality rate; high economic burden and longer hospital ... Conjugating plasmids into bacteria; Tri Parental.

  20. New Conjugates of Quinoxaline as Potent Antitubercular and Antibacterial Agents

    Directory of Open Access Journals (Sweden)

    Ramalingam Peraman

    2016-01-01

    Full Text Available Considering quinoxaline as a privileged structure for the design of potent intercalating agents, some new sugar conjugates of quinoxaline were synthesized and characterized by IR, 1HNMR, 13C NMR, and mass spectral data. In vitro testing for antitubercular and antimicrobial activities was performed against Mycobacterium tuberculosis H37Rv and some pathogenic bacteria. Results revealed that conjugate containing ribose moiety demonstrated the most promising activity against Mycobacteria and bacteria with minimum inhibitory concentrations (MIC of 0.65 and 2.07 μM, respectively. Other conjugates from xylose, glucose, and mannose were moderately active whilst disaccharides conjugates were found to be less active. In silico docking analysis of prototype compound revealed that ATP site of DNA gyrase B subunit could be a possible site for inhibitory action of these synthesized compounds.

  1. New Conjugates of Quinoxaline as Potent Antitubercular and Antibacterial Agents.

    Science.gov (United States)

    Peraman, Ramalingam; Kuppusamy, Rajendran; Killi, Sunil Kumar; Reddy, Y Padmanabha

    2016-01-01

    Considering quinoxaline as a privileged structure for the design of potent intercalating agents, some new sugar conjugates of quinoxaline were synthesized and characterized by IR, (1)HNMR, (13)C NMR, and mass spectral data. In vitro testing for antitubercular and antimicrobial activities was performed against Mycobacterium tuberculosis H 37 Rv and some pathogenic bacteria. Results revealed that conjugate containing ribose moiety demonstrated the most promising activity against Mycobacteria and bacteria with minimum inhibitory concentrations (MIC) of 0.65 and 2.07 μM, respectively. Other conjugates from xylose, glucose, and mannose were moderately active whilst disaccharides conjugates were found to be less active. In silico docking analysis of prototype compound revealed that ATP site of DNA gyrase B subunit could be a possible site for inhibitory action of these synthesized compounds.

  2. Conjugated Polymers/DNA Hybrid Materials for Protein Inactivation.

    Science.gov (United States)

    Zhao, Likun; Zhang, Jiangyan; Xu, Huiming; Geng, Hao; Cheng, Yongqiang

    2016-09-01

    Chromophore-assisted light inactivation (CALI) is a powerful tool for analyzing protein functions due to the high degree of spatial and temporal resolution. In this work, we demonstrate a CALI approach based on conjugated polymers (CPs)/DNA hybrid material for protein inactivation. The target protein is conjugated with single-stranded DNA in advance. Single-stranded DNA can form CPs/DNA hybrid material with cationic CPs via electrostatic and hydrophobic interactions. Through the formation of CPs/DNA hybrid material, the target protein that is conjugated with DNA is brought into close proximity to CPs. Under irradiation, CPs harvest light and generate reactive oxygen species (ROS), resulting in the inactivation of the adjacent target protein. This approach can efficiently inactivate any target protein which is conjugated with DNA and has good specificity and universality, providing a new strategy for studies of protein function and adjustment of protein activity.

  3. Preparation of Conjugated Linoleic Acid and Identification of Its Isomers

    Institute of Scientific and Technical Information of China (English)

    郭诤; 张根旺; 孙彦

    2003-01-01

    Conjugated linoleic acid(CLA)is a kind of fatty acid with physiological activities and potential appli-cation prospect ,A synthesis method of conjugated linoleic acid and a purification technology were studied .CLA was prepared and purified by urea-complexation and conjugation using safflower oil as raw material,The purity of CLA and total recovery of the product was more than 95% and 48%,respectively,The main isomers produced in alkali-catalyzed conjugation were identified by gas chromatography (GC)linked to mass spectrometry(MS) and Fourier transform infrared spectroscopy(FTIR),The total amount of the two main isomers (9cis,11trans-and 10trans,12cis-CLA) determined by GC was more than 90% of the product.

  4. Band-structure engineering in conjugated 2D polymers.

    Science.gov (United States)

    Gutzler, Rico

    2016-10-26

    Conjugated polymers find widespread application in (opto)electronic devices, sensing, and as catalysts. Their common one-dimensional structure can be extended into the second dimension to create conjugated planar sheets of covalently linked molecules. Extending π-conjugation into the second dimension unlocks a new class of semiconductive polymers which as a consequence of their unique electronic properties can find usability in numerous applications. In this article the theoretical band structures of a set of conjugated 2D polymers are compared and information on the important characteristics band gap and valence/conduction band dispersion is extracted. The great variance in these characteristics within the investigated set suggests 2D polymers as exciting materials in which band-structure engineering can be used to tailor sheet-like organic materials with desired electronic properties.

  5. "Angle" Operator Conjugate to Photon's Intrinsic Angular Momentum

    Institute of Scientific and Technical Information of China (English)

    范洪义

    2001-01-01

    We find the correct "angle" operator conjugate to the intrinsic angular momentum of the photon by introducing a suitable representation which involves both left-handed and right-handed polarization photon operators.

  6. Partial Hermitian Conjugate Separability Criteria for Pure Quantum States

    Institute of Scientific and Technical Information of China (English)

    ZHAO Xin; WU Hua; LI Yan-Song; LONG Gui-Lu

    2009-01-01

    We propose a criterion for the separability of quantum pure states using the concept of a partial Hermitian conjugate.It is equivalent to the usual positive partial transposition criteria,with a simple physical interpretation.

  7. Polylactide conjugates of camptothecin with different drug release abilities.

    Science.gov (United States)

    Oledzka, Ewa; Horeglad, Paweł; Gruszczyńska, Zuzanna; Plichta, Andrzej; Nałęcz-Jawecki, Grzegorz; Sobczak, Marcin

    2014-11-25

    Camptothecin-polylactide conjugates (CMPT-PLA) were synthesized by covalent incorporation of CMPT into PLA of different microstructure, i.e., atactic PLA and atactic-block-isotactically enriched PLA (Pm = 0.79) via urethane bonds. The kinetic release of CPMT from CMPT-PLA conjugates, tested in vitro under different conditions, is possible in both cases and notably, strongly dependent on PLA microstructure. It shows that release properties of drug-PLA conjugates can be tailored by controlled design of the PLA microstructure, and allow in the case of CMPT-PLA conjugates for the development of highly controlled biodegradable CMPT systems-important delivery systems for anti-cancer agents.

  8. Polylactide Conjugates of Camptothecin with Different Drug Release Abilities

    Directory of Open Access Journals (Sweden)

    Ewa Oledzka

    2014-11-01

    Full Text Available Camptothecin-polylactide conjugates (CMPT-PLA were synthesized by covalent incorporation of CMPT into PLA of different microstructure, i.e., atactic PLA and atactic-block-isotactically enriched PLA (Pm = 0.79 via urethane bonds. The kinetic release of CPMT from CMPT-PLA conjugates, tested in vitro under different conditions, is possible in both cases and notably, strongly dependent on PLA microstructure. It shows that release properties of drug-PLA conjugates can be tailored by controlled design of the PLA microstructure, and allow in the case of CMPT-PLA conjugates for the development of highly controlled biodegradable CMPT systems—important delivery systems for anti-cancer agents.

  9. A Restarted Conjugate Gradient Method for Ill-posed Problems

    Institute of Scientific and Technical Information of China (English)

    Yan-fei Wang

    2003-01-01

    This paper presents a restarted conjugate gradient iterative algorithm for solving ill-posed problems.The damped Morozov's discrepancy principle is used as a stopping rule. Numerical experiments are given to illustrate the efficiency of the method.

  10. Fluoridated hydroxyapatite: Eu3+ nanorods-loaded folate-conjugated D-α-tocopheryl polyethylene glycol succinate (vitamin E TPGS) micelles for targeted imaging of cancer cells

    Science.gov (United States)

    Wan, Dong; Liu, Weijiao; Wang, Lei; Wang, Hao; Pan, Jie

    2016-03-01

    In this study, fluoridated hydroxyapatite: Eu3+ nanorod-loaded folate-conjugated TPGS micelles were prepared by thin-film hydration. The findings in this study demonstrate that micelles show improved dispersion, high stability, and excellent fluorescent property in aqueous solutions, suitable for targeted imaging of cancer cells with over-expressing folate receptors on their surface. The micelles designed in this study will be a promising tool for early detection of cancer.

  11. Charge Transport in Conjugated Block Copolymers

    Science.gov (United States)

    Smith, Brandon; Le, Thinh; Lee, Youngmin; Gomez, Enrique

    Interest in conjugated block copolymers for high performance organic photovoltaic applications has increased considerably in recent years. Polymer/fullerene mixtures for conventional bulk heterojunction devices, such as P3HT:PCBM, are severely limited in control over interfaces and domain length scales. In contrast, microphase separated block copolymers self-assemble to form lamellar morphologies with alternating electron donor and acceptor domains, thereby maximizing electronic coupling and local order at interfaces. Efficiencies as high as 3% have been reported in solar cells for one block copolymer, P3HT-PFTBT, but the details concerning charge transport within copolymers have not been explored. To fill this gap, we probed the transport characteristics with thin-film transistors. Excellent charge mobility values for electron transport have been observed on aluminum source and drain contacts in a bottom gate, bottom contact transistor configuration. Evidence of high mobility in ordered PFTBT phases has also been obtained following thermal annealing. The insights gleaned from our investigation serve as useful guideposts, revealing the significance of the interplay between charge mobility, interfacial order, and optimal domain size in organic block copolymer semiconductors.

  12. DNA Interaction Studies of Selected Polyamine Conjugates

    Directory of Open Access Journals (Sweden)

    Marta Szumilak

    2016-09-01

    Full Text Available The interaction of polyamine conjugates with DNA double helix has been studied. Binding properties were examined by ethidium bromide (EtBr displacement and DNA unwinding/topoisomerase I/II (Topo I/II activity assays, as well as dsDNA thermal stability studies and circular dichroism spectroscopy. Genotoxicity of the compounds was estimated by a comet assay. It has been shown that only compound 2a can interact with dsDNA via an intercalative binding mode as it displaced EtBr from the dsDNA-dye complex, with Kapp = 4.26 × 106 M−1; caused an increase in melting temperature; changed the circular dichroism spectrum of dsDNA; converted relaxed plasmid DNA into a supercoiled molecule in the presence of Topo I and reduced the amount of short oligonucleotide fragments in the comet tail. Furthermore, preliminary theoretical study has shown that interaction of the discussed compounds with dsDNA depends on molecule linker length and charge distribution over terminal aromatic chromophores.

  13. Microfluidic Fabrication of Conjugated Polymer Sensor Fibers

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Imsung; Song, Simon [Hanyang University, Seoul (Korea, Republic of)

    2014-10-15

    We propose a fabrication method for polydiacetylene (PDA)-embedded hydrogel microfibers on a microfluidic chip. These fibers can be applied to the detection of cyclodextrines (CDs), which are a family of sugar and aluminum ions. PDA, a family of conjugated polymers, has unique characteristics when used for a sensor, because it undergoes a blue-to-red color transition and nonfluorescence-to-fluorescence transition in response to environmental stimulation. PDAs have different sensing characteristics depending on the head group of PCDA. By taking advantage of ionic crosslinking-induced hydrogel formation and the 3D hydrodynamic focusing effect on a microfluidic chip, PCDA-EDEA-derived diacetylene (DA) monomer-embedded microfibers were successfully fabricated. UV irradiation of the fibers afforded blue-colored PDA, and the resulting blue PDA fibers underwent a phase transition to red and emitted red fluorescence upon exposure to CDs and aluminum ions. Their fluorescence intensity varied depending on the CDs and aluminum ion concentrations. This phase transition was also observed when the fibers were dried.

  14. Stellar photometry with Multi Conjugate Adaptive Optics

    CERN Document Server

    Fiorentino, Giuliana; McConnachie, Alan; Stetson, Peter B; Bono, Giuseppe; Turri, Paolo; Andersen, David; Veran, Jean-Pierre; Diolaiti, Emiliano; Schreiber, Laura; Ciliegi, Paolo; Bellazzini, Michele; Tolstoy, Eline; Monelli, Matteo; Iannicola, Giacinto; Ferraro, Ivan; Testa, Vincenzo

    2016-01-01

    We overview the current status of photometric analyses of images collected with Multi Conjugate Adaptive Optics (MCAO) at 8-10m class telescopes that operated, or are operating, on sky. Particular attention will be payed to resolved stellar population studies. Stars in crowded stellar systems, such as globular clusters or in nearby galaxies, are ideal test particles to test AO performance. We will focus the discussion on photometric precision and accuracy reached nowadays. We briefly describe our project on stellar photometry and astrometry of Galactic globular clusters using images taken with GeMS at the Gemini South telescope. We also present the photometry performed with DAOPHOT suite of programs into the crowded regions of these globulars reaching very faint limiting magnitudes Ks ~21.5 mag on moderately large fields of view (~1.5 arcmin squared). We highlight the need for new algorithms to improve the modeling of the complex variation of the Point Spread Function across the ?eld of view. Finally, we outl...

  15. DNA Interaction Studies of Selected Polyamine Conjugates

    Science.gov (United States)

    Szumilak, Marta; Merecz, Anna; Strek, Malgorzata; Stanczak, Andrzej; Inglot, Tadeusz W.; Karwowski, Boleslaw T.

    2016-01-01

    The interaction of polyamine conjugates with DNA double helix has been studied. Binding properties were examined by ethidium bromide (EtBr) displacement and DNA unwinding/topoisomerase I/II (Topo I/II) activity assays, as well as dsDNA thermal stability studies and circular dichroism spectroscopy. Genotoxicity of the compounds was estimated by a comet assay. It has been shown that only compound 2a can interact with dsDNA via an intercalative binding mode as it displaced EtBr from the dsDNA-dye complex, with Kapp = 4.26 × 106 M−1; caused an increase in melting temperature; changed the circular dichroism spectrum of dsDNA; converted relaxed plasmid DNA into a supercoiled molecule in the presence of Topo I and reduced the amount of short oligonucleotide fragments in the comet tail. Furthermore, preliminary theoretical study has shown that interaction of the discussed compounds with dsDNA depends on molecule linker length and charge distribution over terminal aromatic chromophores. PMID:27657041

  16. Aptamer conjugated magnetic nanoparticles as nanosurgeons

    Science.gov (United States)

    Nair, Baiju G.; Nagaoka, Yutaka; Morimoto, Hisao; Yoshida, Yasuhiko; Maekawa, Toru; Sakthi Kumar, D.

    2010-11-01

    Magnetic nanoparticles have shown promise in the fields of targeted drug delivery, hyperthermia and magnetic resonance imaging (MRI) in cancer therapy. The ability of magnetic nanoparticles to undergo surface modification and the effect of external magnetic field in the dynamics of their movement make them an excellent nanoplatform for cancer destruction. Surgical removal of cancerous or unwanted cells selectively from the interior of an organ or tissue without any collateral damage is a serious problem due to the highly infiltrative nature of cancer. To address this problem in surgery, we have developed a nanosurgeon for the selective removal of target cells using aptamer conjugated magnetic nanoparticles controlled by an externally applied three-dimensional rotational magnetic field. With the help of the nanosurgeon, we were able to perform surgical actions on target cells in in vitro studies. LDH and intracellular calcium release assay confirmed the death of cancer cells due to the action of the nanosurgeon which in turn nullifies the possibility of proliferation by the removed cells. The nanosurgeon will be a useful tool in the medical field for selective surgery and cell manipulation studies. Additionally, this system could be upgraded for the selective removal of complex cancers from diverse tissues by incorporating various target specific ligands on magnetic nanoparticles.

  17. Synthesis of arylpyrazole linked benzimidazole conjugates as potential microtubule disruptors.

    Science.gov (United States)

    Kamal, Ahmed; Shaik, Anver Basha; Polepalli, Sowjanya; Kumar, G Bharath; Reddy, Vangala Santhosh; Mahesh, Rasala; Garimella, Srujana; Jain, Nishant

    2015-03-01

    In an attempt to develop potent and selective anticancer agents, a series of twenty arylpyrazole linked benzimidazole conjugates (10a-t) were designed and synthesized as microtubule destabilizing agents. The joining of arylpyrazole to the benzimidazole moiety resulted in a four ring (A, B, C and D) molecular scaffold that comprises of polar heterocyclic rings in the middle associated with rotatable single bonds and substituted aryl rings placed in the opposite directions. These conjugates were evaluated for their ability to inhibit the growth of sixty cancer cell line panel of the NCI. Among these some conjugates like 10a, 10b, 10d, 10e, 10p and 10r exhibited significant growth inhibitory activity against most of the cell lines ranging from 0.3 to 13μM. Interestingly, the conjugate 10b with methoxy group on D-ring expressed appreciable cytotoxic potential. A549 cells treated with some of the potent conjugates like 10a, 10b and 10d arrested cells at G2/M phase apart from activating cyclin-B1 protein levels and disrupting microtubule network. Moreover, these conjugates effectively inhibited tubulin polymerization with IC50 values of 1.3-3.8μM. Whereas, the caspase assay revealed that they activate the casepase-3 leading to apoptosis. Particularly 10b having methoxy substituent induced activity almost 3 folds higher than CA-4. Furthermore, a competitive colchicine binding assay and molecular modeling analysis suggests that these conjugates bind to the tubulin successfully at the colchicine binding site. These investigations reveal that such conjugates having pyrazole and benzimidazole moieties have the potential in the development of newer chemotherapeutic agents.

  18. Optimised deconjugation of androgenic steroid conjugates in bovine urine

    DEFF Research Database (Denmark)

    Pedersen, Mikael; Frandsen, Henrik Lauritz; Andersen, Jens Hinge

    2017-01-01

    with selected aliphatic steroid sulphates (boldenone sulphate, nortestosteron sulphate and testosterone sulphate), and the method was validated for analysis of androgenic steroids in bovine urine using free steroids, steroid sulphates and steroid glucuronides as standards. Glucuronidase and sulphuric acid......After administration of steroids to animals the steroids are partially metabolised in the liver and kidney to phase 2 metabolites, i.e., glucuronic acid or sulphate conjugates. During analysis these conjugated metabolites are normally deconjugated enzymatically with aryl sulphatase...

  19. Cross-conjugation and quantum interference: a general correlation?

    DEFF Research Database (Denmark)

    Valkenier, Hennie; Guedon, Constant M.; Markussen, Troels

    2014-01-01

    We discuss the relationship between the pi-conjugation pattern, molecular length, and charge transport properties of molecular wires, both from an experimental and a theoretical viewpoint. Specifically, we focus on the role of quantum interference in the conductance properties of cross-conjugated...... interference occurs can be tuned by the choice of side group. The latter provides an outlook for future devices in this fascinating field connecting chemistry and physics....

  20. A NOTE ON THE NONLINEAR CONJUGATE GRADIENT METHOD

    Institute of Scientific and Technical Information of China (English)

    Yu-hong Dai; Ya-xiang Yuan

    2002-01-01

    The conjugate gradient method for unconstrained optimization problems varies with a scalar. In this note, a general condition concerning the scalar is given, which ensures the global convergence of the method in the case of strong Wolfe line searches. It is also discussed how to use the result to obtain the convergence of the famous Fletcher-Reeves, and Polak-Ribiere-Polyak conjugate gradient methods. That the condition cannot be relaxed in some sense is mentioned.

  1. Solid State NMR and Fluorescence Studies of Conjugated Polymer Nanocomposties

    Institute of Scientific and Technical Information of China (English)

    Chao Jun JING; Liu Sheng CHEN; Yi SHI; Xi Gao JIN

    2005-01-01

    13C spin-lattice relaxation times (T1) of a conjugated polymer MEH-PPV in polymer/layered silicate nanocomposites together with the steady state fluorescence emission and transient fluorescence decay measurements have been investigated. The T1 values of the conjugated carbons decrease dramatically according to the reduction of polymer concentration in the nano composites, while the fluorescence life times (τ) show a linear prolonging tendency. The results are explained from the point of view of molecular dynamics.

  2. Various methods of gold nanoparticles (GNPs conjugation to antibodies

    Directory of Open Access Journals (Sweden)

    Mir Hadi Jazayeri

    2016-07-01

    These applications require an increasingly complex level of surface decoration in order to achieve efficacy, and limit off-target toxicity. This review will discuss the chemical and physical approaches commonly utilized in relation to surface decoration and the powerful system used to indicate success of the conjugation. Finally, we review the range of recent studies about covalent and noncovalent modes for conjugation of antibodies to the particle surface that aim to advance gold nanoparticle treatments and diagnostics toward the clinic.

  3. Conjugate Representations and Characterizing Escort Expectations in Information Geometry

    Directory of Open Access Journals (Sweden)

    Tatsuaki Wada

    2017-06-01

    Full Text Available Based on the maximum entropy (MaxEnt principle for a generalized entropy functional and the conjugate representations introduced by Zhang, we have reformulated the method of information geometry. For a set of conjugate representations, the associated escort expectation is naturally introduced and characterized by the generalized score function which has zero-escort expectation. Furthermore, we show that the escort expectation induces a conformal divergence.

  4. Conjugate priors for generalized MaxEnt families

    Science.gov (United States)

    van Rooyen, Brendan; Reid, Mark D.

    2014-12-01

    Bayes theorem can be seen as the result of an optimization problem. By slightly altering this optimization problem many generalized Bayes rules can be constructed. In this work we show that a notion of a conjugate prior for non exponential family distributions can be recovered if one uses one of these generalized rules. We prove some theorems concerning this new updating rule before giving a simple example of such a generalized conjugate prior.

  5. Synthesis of Conjugated Polymers for Light Emitting and Photovoltalc Applications

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    1 Results The initial report of polymeric light-emitting diodes (PLEDs) based on poly(p-phenylenevinylene) gave birth to an intense research effort in conjugated polymers, primarily focused on the development of optoelectronic and electrochemical devices. Significant developments in modern synthetic chemistry, especially the chemistry of carbon-carbon bond formation have allowed the synthesis of various well-defined conjugated polymers and oligomers with optimized physical properties.Meanwhile, these re...

  6. Synthesis and characterization of covalent diphenylalanine nanotube-folic acid conjugates

    Science.gov (United States)

    Castillo, John J.; Rindzevicius, Tomas; Wu, Kaiyu; Schmidt, Michael S.; Janik, Katarzyna A.; Boisen, Anja; Svendsen, Winnie; Rozlosnik, Noemi; Castillo-León, Jaime

    2014-07-01

    Herein, we describe the synthesis and characterization of a covalent nanoscale assembly formed between diphenylalanine micro/nanotubes (PNT) and folic acid (FA). The conjugate was obtained via chemical functionalization through coupling of amine groups of PNTs and carboxylic groups of FA. The surface analysis of PNT-FA indicated the presence of FA aggregates on the surface of PNTs. The covalent interaction between FA and self-assembled PNTs was further investigated using fluorescence microscopy, Raman and surface-enhanced Raman scattering (SERS) spectroscopies. The SERS experiments were performed on a large area silver-capped (diameter of 62 nm) silicon nanopillars with an approximate height of 400 nm and a width of 200 nm. The results showed that the PNT-FA synthesis procedure preserves the molecular structure of FA. The PNT-FA conjugate presented in this study is a promising candidate for applications in the detection and diagnosis of cancer or tropical diseases such as leishmaniasis and as a carrier nanosystem delivering drugs to malignant tumors that overexpress folate receptors.

  7. Sodium alginate conjugated graphene oxide as a new carrier for drug delivery system.

    Science.gov (United States)

    Fan, Lihong; Ge, Hongyu; Zou, Shengqiong; Xiao, Yao; Wen, Huigao; Li, Ya; Feng, Han; Nie, Min

    2016-12-01

    The biomedical applications of graphene-based materials, including drug delivery, have grown rapidly in the past few years. The aim of this present study is to enhance the efficiency and specificity of anticancer drug delivery and realize intelligently controlled release and targeted delivery. Graphene oxide (GO) was first prepared from purified natural graphite according to a modified Hummers' method. Then GO was functionalized with adipic acid dihydrazide to introduce amine groups, and sodium alginate (SA) was covalently conjugated to GO by the formation of amide bonds. The resulting GO-SA conjugate was characterized and used as a carrier to encapsulate the anticancer drug doxorubicin hydrochloride (DOX·HCl) to study in vitro release behavior. The maximum loading capacity of DOX on GO-SA was 1.843mg/mg and the drug release rate under tumor cell microenvironment of pH 5.0 was significantly higher than that under physiological conditions of pH 6.5 and 7.4. Methylthiazol tetrazolium (MTT) assay was applied to evaluate the Hela cells and NIH-3T3 cells cytotoxicity of GO-SA. Results showed that GO-SA had no obvious toxicity and GO-SA/DOX exhibits notable cytotoxicity to Hela cells. Cell uptake studies indicated that GO-SA could specifically transport the DOX into Hela cells over-expressing CD44 receptors and showed enhanced toxicity. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Methotrexate-conjugated quantum dots: synthesis, characterisation and cytotoxicity in drug resistant cancer cells.

    Science.gov (United States)

    Johari-Ahar, Mohammad; Barar, Jaleh; Alizadeh, Ali Mohammad; Davaran, Soodabeh; Omidi, Yadollah; Rashidi, Mohammad-Reza

    2016-01-01

    Methotrexate (MTX), a folic acid derivative, is a potent anticancer used for treatment of different malignancies, but possible initiation of drug resistance to MTX by cancer cells has limited its applications. Nanoconjugates (NCs) of MTX to quantum dots (QDs) may favour the cellular uptake via folate receptors (FRs)-mediated endocytosis that circumvents the efflux functions of cancer cells. We synthesised MTX-conjugated l-cysteine capped CdSe QDs (MTX-QD nanoconjugates) and evaluated their internalisation and cytotoxicity in the KB cells with/without resistancy to MTX. The NCs were fully characterised by high resolution transmission electron microscopy (HR-TEM), atomic force microscopy (AFM), dynamic light scattering (DLS) and optical spectroscopy. Upon conjugation with MTX, the photoluminescence (PL) properties of QDs altered, while an obvious quenching in PL of QDs was observed after physical mixing. The MTX-QD nanoconjugates efficiently internalised into the cancer cells, and induced markedly high cytotoxicity (IC50, 12.0 µg/mL) in the MTX-resistant KB cells as compared to the free MTX molecules (IC50,105.0 µg/mL), whereas, these values were respectively about 7.0 and 0.6 µg/mL in the MTX-sensitive KB cells. Based on these findings, the MTX-QD nanoconjugates are proposed for the targeted therapy of MTX-resistant cancers, which may provide an improved outcome in the relapsed FR-overexpressing cancers.

  9. Polydopamine-Coated Porous Microspheres Conjugated with Immune Stimulators for Enhanced Cytokine Induction in Macrophages.

    Science.gov (United States)

    Jang, Hyo-Eun; Mok, Hyejung

    2016-11-01

    Polydopamine-coated porous microsphere (PPM) is investigated as a simple and versatile immobilization strategy for immune-stimulating biomolecules to enhance delivery efficiency and immune-stimulating effects such as cytokine induction in macrophages. The PPMs, with diameters of about 2 μm, exhibit simultaneous and efficient incorporation of biomolecules (nucleotides and proteins), which is comparable to that achieved using microspheres carrying biomolecules internally by virtue of their porous structure. Ovalbumin-conjugated PPMs are internalized into macrophages efficiently and selectively via the phagocytic pathway, without any noticeable toxicity. Internalized CpG oligodeoxynucleotide (ODN)-conjugated PPMs (PPM-CpG) greatly enhance the induction of selected cytokines (TNF-α and IL-6) in RAW 264.7 cells compared to that by the soluble CpG ODN and ionic complexes. Therefore, PPMs generated in this study may serve as effective carriers of immune-stimulating biomolecules such as diverse toll-like receptor agonists. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize

    Science.gov (United States)

    Adams, Stephen R.; Yang, Howard C.; Savariar, Elamprakash N.; Aguilera, Joe; Crisp, Jessica L.; Jones, Karra A.; Whitney, Michael A.; Lippman, Scott M.; Cohen, Ezra E. W.; Tsien, Roger Y.; Advani, Sunil J.

    2016-01-01

    Tumour resistance to radiotherapy remains a barrier to improving cancer patient outcomes. To overcome radioresistance, certain drugs have been found to sensitize cells to ionizing radiation (IR). In theory, more potent radiosensitizing drugs should increase tumour kill and improve patient outcomes. In practice, clinical utility of potent radiosensitizing drugs is curtailed by off-target side effects. Here we report potent anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize to tumours based on surface receptor expression. While two classes of potent anti-tubulins, auristatins and maytansinoids, indiscriminately radiosensitize tumour cells, conjugating these potent anti-tubulins to anti-ErbB antibodies restrict their radiosensitizing capacity. Of translational significance, we report that a clinically used maytansinoid ADC, ado-trastuzumab emtansine (T-DM1), with IR prolongs tumour control in target expressing HER2+ tumours but not target negative tumours. In contrast to ErbB signal inhibition, our findings establish an alternative therapeutic paradigm for ErbB-based radiosensitization using antibodies to restrict radiosensitizer delivery. PMID:27698471

  11. Evaluation of Anti-Inflammatory Drug-Conjugated Silicon Quantum Dots: Their Cytotoxicity and Biological Effect

    Directory of Open Access Journals (Sweden)

    Kenji Yamamoto

    2013-01-01

    Full Text Available Silicon quantum dots (Si-QDs have great potential for biomedical applications, including their use as biological fluorescent markers and carriers for drug delivery systems. Biologically inert Si-QDs are less toxic than conventional cadmium-based QDs, and can modify the surface of the Si-QD with covalent bond. We synthesized water-soluble alminoprofen-conjugated Si-QDs (Ap-Si. Alminoprofen is a non-steroid anti-inflammatory drug (NSAID used as an analgesic for rheumatism. Our results showed that the “silicon drug” is less toxic than the control Si-QD and the original drug. These phenomena indicate that the condensed surface integration of ligand/receptor-type drugs might reduce the adverse interaction between the cells and drug molecules. In addition, the medicinal effect of the Si-QDs (i.e., the inhibition of COX-2 enzyme was maintained compared to that of the original drug. The same drug effect is related to the integration ratio of original drugs, which might control the binding interaction between COX-2 and the silicon drug. We conclude that drug conjugation with biocompatible Si-QDs is a potential method for functional pharmaceutical drug development.

  12. Chemical conjugate TMV-peptide bivalent fusion vaccines improve cellular immunity and tumor protection.

    Science.gov (United States)

    McCormick, Alison A; Corbo, Tina A; Wykoff-Clary, Sherri; Palmer, Kenneth E; Pogue, Gregory P

    2006-01-01

    Chemical conjugation of CTL peptides to tobacco mosaic virus (TMV) has shown promise as a molecular adjuvant scaffold for augmentation of cellular immune responses to peptide vaccines. This study demonstrates the ease of generating complex multipeptide vaccine formulations using chemical conjugation to TMV for improved vaccine efficacy. We have tested a model foreign antigen target-the chicken ovalbumin-derived CTL peptide (Ova peptide), as well as mouse melanoma-associated CTL epitopes p15e and tyrosinase-related protein 2 (Trp2) peptides that are self-antigen targets. Ova peptide fusions to TMV, as bivalent formulations with peptides encoding additional T-help or cellular uptake via the integrin-receptor binding RGD peptide, showed improved vaccine potency evidenced by significantly enhanced numbers of antigen-reactive T cells measured by in vitro IFNgamma cellular analysis. We measured the biologically relevant outcome of vaccination in protection of mice from EG.7-Ova tumor challenge, which was achieved with only two doses of vaccine ( approximately 600 ng peptide) given without adjuvant. The p15e peptide alone or Trp2 peptide alone, or as a bivalent formulation with T-help or RGD uptake epitopes, was unable to stimulate effective tumor protection. However, a vaccine with both CTL peptides fused together onto TMV generated significantly improved survival. Interestingly, different bivalent vaccine formulations were required to improve vaccine efficacy for Ova or melanoma tumor model systems.

  13. Half-sandwich ruthenium(II) biotin conjugates as biological vectors to cancer cells.

    Science.gov (United States)

    Babak, Maria V; Plażuk, Damian; Meier, Samuel M; Arabshahi, Homayon John; Reynisson, Jóhannes; Rychlik, Błażej; Błauż, Andrzej; Szulc, Katarzyna; Hanif, Muhammad; Strobl, Sebastian; Roller, Alexander; Keppler, Bernhard K; Hartinger, Christian G

    2015-03-23

    Ruthenium(II)-arene complexes with biotin-containing ligands were prepared so that a novel drug delivery system based on tumor-specific vitamin-receptor mediated endocytosis could be developed. The complexes were characterized by spectroscopic methods and their in vitro anticancer activity in cancer cell lines with various levels of major biotin receptor (COLO205, HCT116 and SW620 cells) was tested in comparison with the ligands. In all cases, coordination of ruthenium resulted in significantly enhanced cytotoxicity. The affinity of Ru(II) -biotin complexes to avidin was investigated and was lower than that of unmodified biotin. Hill coefficients in the range 2.012-2.851 suggest strong positive cooperation between the complexes and avidin. To estimate the likelihood of binding to the biotin receptor/transporter, docking studies with avidin and streptavidin were conducted. These explain, to some extent, the in vitro anticancer activity results and support the conclusion that these novel half-sandwich ruthenium(II)-biotin conjugates may act as biological vectors to cancer cells, although no clear relationship between the cellular Ru content, the cytotoxicity, and the presence of the biotin moiety was observed.

  14. Intranuclear targeting and nuclear export of the adenovirus E1B-55K protein are regulated by SUMO1 conjugation

    OpenAIRE

    Kindsmüller, Kathrin; Groitl, Peter; Härtl, Barbara; Blanchette, Paola; Hauber, Joachim; Dobner, Thomas

    2007-01-01

    We have investigated the requirements for CRM1-mediated nuclear export and SUMO1 conjugation of the adenovirus E1B-55K protein during productive infection. Our data show that CRM1 is the major export receptor for E1B-55K in infected cells. Functional inactivation of the E1B-55K CRM1-dependent nuclear export signal (NES) or leptomycin B treatment causes an almost complete redistribution of the viral protein from the cytoplasm to the nucleus and its accumulation at the periphery of the viral re...

  15. Chimeric Antisense Oligonucleotide Conjugated to α-Tocopherol

    Directory of Open Access Journals (Sweden)

    Tomoko Nishina

    2015-01-01

    Full Text Available We developed an efficient system for delivering short interfering RNA (siRNA to the liver by using α-tocopherol conjugation. The α-tocopherol–conjugated siRNA was effective and safe for RNA interference–mediated gene silencing in vivo. In contrast, when the 13-mer LNA (locked nucleic acid-DNA gapmer antisense oligonucleotide (ASO was directly conjugated with α-tocopherol it showed markedly reduced silencing activity in mouse liver. Here, therefore, we tried to extend the 5′-end of the ASO sequence by using 5′-α-tocopherol–conjugated 4- to 7-mers of unlocked nucleic acid (UNA as a “second wing.” Intravenous injection of mice with this α-tocopherol–conjugated chimeric ASO achieved more potent silencing than ASO alone in the liver, suggesting increased delivery of the ASO to the liver. Within the cells, the UNA wing was cleaved or degraded and α-tocopherol was released from the 13-mer gapmer ASO, resulting in activation of the gapmer. The α-tocopherol–conjugated chimeric ASO showed high efficacy, with hepatic tropism, and was effective and safe for gene silencing in vivo. We have thus identified a new, effective LNA-DNA gapmer structure in which drug delivery system (DDS molecules are bound to ASO with UNA sequences.

  16. O:2-CRM(197) conjugates against Salmonella Paratyphi A.

    Science.gov (United States)

    Micoli, Francesca; Rondini, Simona; Gavini, Massimiliano; Lanzilao, Luisa; Medaglini, Donata; Saul, Allan; Martin, Laura B

    2012-01-01

    Enteric fevers remain a common and serious disease, affecting mainly children and adolescents in developing countries. Salmonella enterica serovar Typhi was believed to cause most enteric fever episodes, but several recent reports have shown an increasing incidence of S. Paratyphi A, encouraging the development of a bivalent vaccine to protect against both serovars, especially considering that at present there is no vaccine against S. Paratyphi A. The O-specific polysaccharide (O:2) of S. Paratyphi A is a protective antigen and clinical data have previously demonstrated the potential of using O:2 conjugate vaccines. Here we describe a new conjugation chemistry to link O:2 and the carrier protein CRM(197), using the terminus 3-deoxy-D-manno-octulosonic acid (KDO), thus leaving the O:2 chain unmodified. The new conjugates were tested in mice and compared with other O:2-antigen conjugates, synthesized adopting previously described methods that use CRM(197) as carrier protein. The newly developed conjugation chemistry yielded immunogenic conjugates with strong serum bactericidal activity against S. Paratyphi A.

  17. Conjugates of 1'-Aminoferrocene-1-carboxylic Acid and Proline: Synthesis, Conformational Analysis and Biological Evaluation

    Directory of Open Access Journals (Sweden)

    Monika Kovačević

    2014-08-01

    Full Text Available Our previous studies showed that alteration of dipeptides Y-Fca-Ala-OMe (III into Y-Ala-Fca-OMe (IV (Y = Ac, Boc; Fca = 1'-aminoferrocene-1-carboxylic acid significantly influenced their conformational space. The novel bioconjugates Y-Fca-Pro-OMe (1, Y = Ac; 2, Y = Boc and Y-Pro-Fca-OMe (3, Y = Boc; 4, Y = Ac have been prepared in order to investigate the influence of proline, a well-known turn-inducer, on the conformational properties of small organometallic peptides with an exchanged constituent amino acid sequences. For this purpose, peptides 1–4 were subjected to detailed spectroscopic analysis (IR, NMR, CD spectroscopy in solution. The conformation of peptide 3 in the solid state was determined. Furthermore, the ability of the prepared conjugates to inhibit the growth of estrogen receptor-responsive MCF-7 mammary carcinoma cells and HeLa cervical carcinoma cells was tested.

  18. Development of a growth-hormone-conjugated nanodiamond complex for cancer therapy.

    Science.gov (United States)

    Chu, Hsueh-Liang; Chen, Hung-Wei; Tseng, Shin-Hua; Hsu, Ming-Hua; Ho, Li-Ping; Chou, Fu-Hsuan; Li, Md Phd Hsing-Yuan; Chang, Yu-Chuan; Chen, Pei-Hsin; Tsai, Li-Yun; Chou, Ching-Chung; Chen, Jyh Shin; Cheng, Tsai-Mu; Chang, Chia-Ching

    2014-05-01

    It is highly desirable to develop a therapeutic, observable nanoparticle complex for specific targeting in cancer therapy. Growth hormone (GH) and its antagonists have been explored as cancer cell-targeting molecules for both imaging and therapeutic applications. In this study, a low toxicity, biocompatible, therapeutic, and observable GH-nanoparticle complex for specifically targeting growth hormone receptor (GHR) in cancer cells was synthesized by conjugating GH with green fluorescence protein and carboxylated nanodiamond. Moreover, we have shown that this complex can be triggered by laser irradiation to create a "nanoblast" and induce cell death in the A549 non-small-cell lung cancer cell line via the apoptotic pathway. This laser-mediated, cancer-targeting platform can be widely used in cancer therapy.

  19. Active Peptide-Conjugated Chitosan Matrices as an Artificial Basement Membrane

    Directory of Open Access Journals (Sweden)

    Kentaro Hozumi

    2015-02-01

    Full Text Available The basement membrane, a thin extracellular matrix, plays a critical role in tissue development and repair. Laminins are the major component of basement membrane and have diverse biological activities. We have identified various cell-adhesive peptides from laminins and their specific cell surface receptors. Polysaccharides, including chitosan, have been used as scaffolds, which regulate cellular functions for tissue engineering. We have developed laminin-derived active peptide-chitosan matrices as functional scaffolds. The biological activity of the peptides was enhanced when the peptides were conjugated to a chitosan matrix, suggesting that the peptide-chitosan matrix approach has an advantage for an active biomaterial. Further, the laminin peptide-chitosan matrices have the potential to mimic the basement membrane and are useful for tissue engineering as an artificial basement membrane.

  20. Degree of approximation of conjugate of Lip $ \\alpha$ class function by $ {K^\\lambda}$-summability means of conjugate series of a Fourier series

    Directory of Open Access Journals (Sweden)

    Shyam Lal

    2003-12-01

    Full Text Available In this paper the degree of approximation of conjugate of a function belonging to Lip $ \\alpha$ class by $ K^\\lambda$-summability means of conjugate series of its Fourier series has been determined.

  1. Selective esterification of non-conjugated carboxylic acids in the presence of conjugated or aromatic carboxylic acids over active carbon supported methanesulfonic acid

    Institute of Scientific and Technical Information of China (English)

    FENG ZeWang; ZHAO XinQi; BI Hua

    2008-01-01

    Non-conjugated carboxylic acids are selectively esterified in good yields in the presence of conjugated or aromatic carboxylic acids by stirring over active carbon supported methanesulfonic acid in dichloromethane at room temperature.

  2. Selective esterification of non-conjugated carboxylic acids in the presence of conjugated or aromatic carboxylic acids over active carbon supported methanesulfonic acid

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Non-conjugated carboxylic acids are selectively esterified in good yields in the presence of conjugated or aromatic carboxylic acids by stirring over active carbon supported methanesulfonic acid in di-chloromethane at room temperature.

  3. Opioid Receptors.

    Science.gov (United States)

    Stein, Christoph

    2016-01-01

    Opioids are the oldest and most potent drugs for the treatment of severe pain. Their clinical application is undisputed in acute (e.g., postoperative) and cancer pain, but their long-term use in chronic pain has met increasing scrutiny. This article reviews mechanisms underlying opioid analgesia and other opioid actions. It discusses the structure, function, and plasticity of opioid receptors; the central and peripheral sites of analgesic actions and side effects; endogenous and exogenous opioid receptor ligands; and conventional and novel opioid compounds. Challenging clinical situations, such as the tension between chronic pain and addiction, are also illustrated.

  4. Synthesis and Characterization of Sodium Alginate Conjugate and Study of Effect of Conjugation on Drug Release from Matrix Tablet.

    Science.gov (United States)

    Satheeshababu, B K; Mohamed, I

    2015-01-01

    The aim of the present research work to study the effect of conjugation of the polymer on drug release from the matrix tablets. Sodium alginate L-cysteine conjugate was achieved by covalent attachment of thiol group of L-cysteine with the primary amino group of sodium alginate through the amide bonds formed by primary amino groups of the sodium alginate and the carboxylic acid group of L-cysteine. The synthesised sodium alginate L-cysteine conjugate was characterised by determining of charring point, Fourier transmission-infrared and differential scanning calorimetric analysis. To study the effect of conjugation on drug release pattern, the matrix tablets were prepared using various proportions of sodium alginate and sodium alginate L-cysteine conjugate along with atorvastatin calcium as model drug. The wet granulation technique was adopted and prepared matrix tablets were evaluated for various physical parameters. The in vitro drug release study results suggested that tablet formulated in combination of sodium alginate and sodium alginate L-cysteine conjugate S4 showed 100% after 8 h drug release whereas formulated with only sodium alginate S0 released 40% in 8 h.

  5. Enhanced Anti-Tumoral Activity of Methotrexate-Human Serum Albumin Conjugated Nanoparticles by Targeting with Luteinizing Hormone-Releasing Hormone (LHRH) Peptide

    Science.gov (United States)

    Taheri, Azade; Dinarvand, Rassoul; Atyabi, Fatemeh; Ahadi, Fatemeh; Nouri, Farank Salman; Ghahremani, Mohammad Hossein; Ostad, Seyed Nasser; Borougeni, Atefeh Taheri; Mansoori, Pooria

    2011-01-01

    Active targeting could increase the efficacy of anticancer drugs. Methotrexate-human serum albumin (MTX-HSA) conjugates, functionalized by luteinizing hormone-releasing hormone (LHRH) as targeting moieties, with the aim of specifically targeting the cancer cells, were prepared. Owing to the high expression of LHRH receptors in many cancer cells as compared to normal cells, LHRH was used as the targeting ligand in this study. LHRH was conjugated to MTX-HSA nanoparticles via a cross-linker. Three types of LHRH targeted nanoparticles with a mean particle size between 120–138 nm were prepared. The cytotoxicity of LHRH targeted and non-targeted nanoparticles were determined on the LHRH positive and negative cell lines. The internalization of the targeted and non-targeted nanoparticles in LHRH receptor positive and negative cells was investigated using flow cytometry analysis and fluorescence microscopy. The cytotoxicity of the LHRH targeted nanoparticles on the LHRH receptor positive cells were significantly more than non-targeted nanoparticles. LHRH targeted nanoparticles were also internalized by LHRH receptor positive cells significantly more than non-targeted nanoparticles. There were no significant differences between the uptake of targeted and non-targeted nanoparticles to the LHRH receptor negative cells. The active targeting procedure using LHRH targeted MTX-HSA nanoparticles could increase the anti-tumoral activity of MTX. PMID:21845098

  6. Enhanced Anti-Tumoral Activity of Methotrexate-Human Serum Albumin Conjugated Nanoparticles by Targeting with Luteinizing Hormone-Releasing Hormone (LHRH Peptide

    Directory of Open Access Journals (Sweden)

    Pooria Mansoori

    2011-07-01

    Full Text Available Active targeting could increase the efficacy of anticancer drugs. Methotrexate-human serum albumin (MTX-HSA conjugates, functionalized by luteinizing hormone-releasing hormone (LHRH as targeting moieties, with the aim of specifically targeting the cancer cells, were prepared. Owing to the high expression of LHRH receptors in many cancer cells as compared to normal cells, LHRH was used as the targeting ligand in this study. LHRH was conjugated to MTX-HSA nanoparticles via a cross-linker. Three types of LHRH targeted nanoparticles with a mean particle size between 120–138 nm were prepared. The cytotoxicity of LHRH targeted and non-targeted nanoparticles were determined on the LHRH positive and negative cell lines. The internalization of the targeted and non-targeted nanoparticles in LHRH receptor positive and negative cells was investigated using flow cytometry analysis and fluorescence microscopy. The cytotoxicity of the LHRH targeted nanoparticles on the LHRH receptor positive cells were significantly more than non-targeted nanoparticles. LHRH targeted nanoparticles were also internalized by LHRH receptor positive cells significantly more than non-targeted nanoparticles. There were no significant differences between the uptake of targeted and non-targeted nanoparticles to the LHRH receptor negative cells. The active targeting procedure using LHRH targeted MTX-HSA nanoparticles could increase the anti-tumoral activity of MTX.

  7. Antibody conjugate radioimmunotherapy of superficial bladder cancer

    Directory of Open Access Journals (Sweden)

    Alan Perkins

    2002-09-01

    Full Text Available The administration of antibody conjugates for cancer therapy is now proving to be of clinical value. We are currently undertaking a programme of clinical studies using the monoclonal antibody C595 (IgG3 which reacts with the MUC1 glycoprotein antigen that is aberrantly expressed in a high proportion of bladder tumours. Radioimmunoconjugates of the C595 antibody have been produced with high radiolabelling efficiency and immunoreactivity using Tc-99m and In-111 for diagnostic imaging, and disease staging and the cytotoxic radionuclides Cu-67 and Re-188 for therapy of superficial bladder cancer. A Phase I/II therapeutic trail involving the intravesical administration of antibody directly into the bladder has now begun.A administração de anticorpos conjugados para o tratamento do câncer está agora provando ser de valor clínico. Nós estamos atualmente realizando um programa de estudos clínicos usando o anticorpo monoclonal C595 (IgG3 que reage com a glicoproteína MUC1 que está aberrantemente expressa numa alta proporção de tumores de bexiga. Tem sido produzidos radioimunoconjugados do anticorpo C595, com alta eficiência de radiomarcação e a imunoreatividade, usando-se o Tc-99m e In-111, para o diagnóstico por imagem e estagiamento de doenças. Tem sido produzidos, também, radionuclídeos citotóxicos (Cu-67 e Re-188 para o tratamento de cânceres superficiais de bexiga. A fase terapêutica I/II já se iniciou, envolvendo a administração intravesical do anticorpo diretamente na bexiga.

  8. Phenylnaphthalenes: sublimation equilibrium, conjugation, and aromatic interactions.

    Science.gov (United States)

    Lima, Carlos F R A C; Rocha, Marisa A A; Schröder, Bernd; Gomes, Lígia R; Low, John N; Santos, Luís M N B F

    2012-03-22

    In this work, the interplay between structure and energetics in some representative phenylnaphthalenes is discussed from an experimental and theoretical perspective. For the compounds studied, the standard molar enthalpies, entropies and Gibbs energies of sublimation, at T = 298.15 K, were determined by the measurement of the vapor pressures as a function of T, using a Knudsen/quartz crystal effusion apparatus. The standard molar enthalpies of formation in the crystalline state were determined by static bomb combustion calorimetry. From these results, the standard molar enthalpies of formation in the gaseous phase were derived and, altogether with computational chemistry at the B3LYP/6-311++G(d,p) and MP2/cc-pVDZ levels of theory, used to deduce the relative molecular stabilities in various phenylnaphthalenes. X-ray crystallographic structures were obtained for some selected compounds in order to provide structural insights, and relate them to energetics. The thermodynamic quantities for sublimation suggest that molecular symmetry and torsional freedom are major factors affecting entropic differentiation in these molecules, and that cohesive forces are significantly influenced by molecular surface area. The global results obtained support the lack of significant conjugation between aromatic moieties in the α position of naphthalene but indicate the existence of significant electron delocalization when the aromatic groups are in the β position. Evidence for the existence of a quasi T-shaped intramolecular aromatic interaction between the two outer phenyl rings in 1,8-di([1,1'-biphenyl]-4-yl)naphthalene was found, and the enthalpy of this interaction quantified on pure experimental grounds as -(11.9 ± 4.8) kJ·mol(-1), in excellent agreement with the literature CCSD(T) theoretical results for the benzene dimer.

  9. Dosing Schedules for Pneumococcal Conjugate Vaccine

    Science.gov (United States)

    2014-01-01

    Since second generation pneumococcal conjugate vaccines (PCVs) targeting 10 and 13 serotypes became available in 2010, the number of national policy makers considering these vaccines has steadily increased. An important consideration for a national immunization program is the timing and number of doses—the schedule—that will best prevent disease in the population. Data on disease epidemiology and the efficacy or effectiveness of PCV schedules are typically considered when choosing a schedule. Practical concerns, such as the existing vaccine schedule, and vaccine program performance are also important. In low-income countries, pneumococcal disease and deaths typically peak well before the end of the first year of life, making a schedule that provides PCV doses early in life (eg, a 6-, 10- and 14-week schedule) potentially the best option. In other settings, a schedule including a booster dose may address disease that peaks in the second year of life or may be seen to enhance a schedule already in place. A large and growing body of evidence from immunogenicity studies, as well as clinical trials and observational studies of carriage, pneumonia and invasive disease, has been systematically reviewed; these data indicate that schedules of 3 or 4 doses all work well, and that the differences between these regimens are subtle, especially in a mature program in which coverage is high and indirect (herd) effects help enhance protection provided directly by a vaccine schedule. The recent World Health Organization policy statement on PCVs endorsed a schedule of 3 primary doses without a booster or, as a new alternative, 2 primary doses with a booster dose. While 1 schedule may be preferred in a particular setting based on local epidemiology or practical considerations, achieving high coverage with 3 doses is likely more important than the specific timing of doses. PMID:24336059

  10. Synergistically enhanced selective intracellular uptake of anticancer drug carrier comprising folic acid-conjugated hydrogels containing magnetite nanoparticles

    Science.gov (United States)

    Kim, Haneul; Jo, Ara; Baek, Seulgi; Lim, Daeun; Park, Soon-Yong; Cho, Soo Kyung; Chung, Jin Woong; Yoon, Jinhwan

    2017-01-01

    Targeted drug delivery has long been extensively researched since drug delivery and release at the diseased site with minimum dosage realizes the effective therapy without adverse side effects. In this work, to achieve enhanced intracellular uptake of anticancer drug carriers for efficient chemo-therapy, we have designed targeted multifunctional anticancer drug carrier hydrogels. Temperature-responsive poly(N-isopropylacrylamide) (PNIPAm) hydrogel core containing superparamagnetic magnetite nanoparticles (MNP) were prepared using precipitation polymerization, and further polymerized with amine-functionalized copolymer shell to facilitate the conjugation of targeting ligand. Then, folic acid, specific targeting ligand for cervical cancer cell line (HeLa), was conjugated on the hydrogel surface, yielding the ligand conjugated hybrid hydrogels. We revealed that enhanced intracellular uptake by HeLa cells in vitro was enabled by both magnetic attraction and receptor-mediated endocytosis, which were contributed by MNP and folic acid, respectively. Furthermore, site-specific uptake of the developed carrier was confirmed by incubating with several other cell lines. Based on synergistically enhanced intracellular uptake, efficient cytotoxicity and apoptotic activity of HeLa cells incubated with anticancer drug loaded hybrid hydrogels were successfully achieved. The developed dual-targeted hybrid hydrogels are expected to provide a platform for the next generation intelligent drug delivery systems.

  11. Self-assembled ternary complexes stabilized with hyaluronic acid-green tea catechin conjugates for targeted gene delivery.

    Science.gov (United States)

    Liang, Kun; Bae, Ki Hyun; Lee, Fan; Xu, Keming; Chung, Joo Eun; Gao, Shu Jun; Kurisawa, Motoichi

    2016-03-28

    Nanosized polyelectrolyte complexes are attractive delivery vehicles for the transfer of therapeutic genes to diseased cells. Here we report the application of self-assembled ternary complexes constructed with plasmid DNA, branched polyethylenimine and hyaluronic acid-green tea catechin conjugates for targeted gene delivery. These conjugates not only stabilize plasmid DNA/polyethylenimine complexes via the strong DNA-binding affinity of green tea catechin, but also facilitate their transport into CD44-overexpressing cells via receptor-mediated endocytosis. The hydrodynamic size, surface charge and physical stability of the complexes are characterized. We demonstrate that the stabilized ternary complexes display enhanced resistance to nuclease attack and polyanion-induced dissociation. Moreover, the ternary complexes can efficiently transfect the difficult-to-transfect HCT-116 colon cancer cell line even in serum-supplemented media due to their enhanced stability and CD44-targeting ability. Confocal microscopic analysis demonstrates that the stabilized ternary complexes are able to promote the nuclear transport of plasmid DNA more effectively than binary complexes and hyaluronic acid-coated ternary complexes. The present study suggests that the ternary complexes stabilized with hyaluronic acid-green tea catechin conjugates can be widely utilized for CD44-targeted delivery of nucleic acid-based therapeutics.

  12. Conjugation of cholesterol to HIV-1 fusion inhibitor C34 increases peptide-membrane interactions potentiating its action.

    Directory of Open Access Journals (Sweden)

    Axel Hollmann

    Full Text Available Recently, the covalent binding of a cholesterol moiety to a classical HIV-1 fusion inhibitor peptide, C34, was shown to potentiate its antiviral activity. Our purpose was to evaluate the interaction of cholesterol-conjugated and native C34 with membrane model systems and human blood cells to understand the effects of this derivatization. Lipid vesicles and monolayers with defined compositions were used as model membranes. C34-cholesterol partitions more to fluid phase membranes that mimic biological membranes. Importantly, there is a preference of the conjugate for liquid ordered membranes, rich in cholesterol and/or sphingomyelin, as observed both from partition and surface pressure studies. In human erythrocytes and peripheral blood mononuclear cells (PBMC, C34-cholesterol significantly decreases the membrane dipole potential. In PBMC, the conjugate was 14- and 115-fold more membranotropic than T-1249 and enfuvirtide, respectively. C34 or cholesterol alone did not show significant membrane activity. The enhanced interaction of C34-cholesterol with biological membranes correlates with its higher antiviral potency. Higher partitions for lipid-raft like compositions direct the drug to the receptor-rich domains where membrane fusion is likely to occur. This intermediary membrane binding step may facilitate the drug delivery to gp41 in its pre-fusion state.

  13. Recent Advances in Conjugated Polymers for Light Emitting Devices

    Directory of Open Access Journals (Sweden)

    Mohan Raja

    2011-03-01

    Full Text Available A recent advance in the field of light emitting polymers has been the discovery of electroluminescent conjugated polymers, that is, kind of fluorescent polymers that emit light when excited by the flow of an electric current. These new generation fluorescent materials may now challenge the domination by inorganic semiconductor materials of the commercial market in light-emitting devices such as light-emitting diodes (LED and polymer laser devices. This review provides information on unique properties of conjugated polymers and how they have been optimized to generate these properties. The review is organized in three sections focusing on the major advances in light emitting materials, recent literature survey and understanding the desirable properties as well as modern solid state lighting and displays. Recently, developed conjugated polymers are also functioning as roll-up displays for computers and mobile phones, flexible solar panels for power portable equipment as well as organic light emitting diodes in displays, in which television screens, luminous traffic, information signs, and light-emitting wallpaper in homes are also expected to broaden the use of conjugated polymers as light emitting polymers. The purpose of this review paper is to examine conjugated polymers in light emitting diodes (LEDs in addition to organic solid state laser. Furthermore, since conjugated polymers have been approved as light-emitting organic materials similar to inorganic semiconductors, it is clear to motivate these organic light-emitting devices (OLEDs and organic lasers for modern lighting in terms of energy saving ability. In addition, future aspects of conjugated polymers in LEDs were also highlighted in this review.

  14. Recent advances in conjugated polymers for light emitting devices.

    Science.gov (United States)

    Alsalhi, Mohamad Saleh; Alam, Javed; Dass, Lawrence Arockiasamy; Raja, Mohan

    2011-01-01

    A recent advance in the field of light emitting polymers has been the discovery of electroluminescent conjugated polymers, that is, kind of fluorescent polymers that emit light when excited by the flow of an electric current. These new generation fluorescent materials may now challenge the domination by inorganic semiconductor materials of the commercial market in light-emitting devices such as light-emitting diodes (LED) and polymer laser devices. This review provides information on unique properties of conjugated polymers and how they have been optimized to generate these properties. The review is organized in three sections focusing on the major advances in light emitting materials, recent literature survey and understanding the desirable properties as well as modern solid state lighting and displays. Recently, developed conjugated polymers are also functioning as roll-up displays for computers and mobile phones, flexible solar panels for power portable equipment as well as organic light emitting diodes in displays, in which television screens, luminous traffic, information signs, and light-emitting wallpaper in homes are also expected to broaden the use of conjugated polymers as light emitting polymers. The purpose of this review paper is to examine conjugated polymers in light emitting diodes (LEDs) in addition to organic solid state laser. Furthermore, since conjugated polymers have been approved as light-emitting organic materials similar to inorganic semiconductors, it is clear to motivate these organic light-emitting devices (OLEDs) and organic lasers for modern lighting in terms of energy saving ability. In addition, future aspects of conjugated polymers in LEDs were also highlighted in this review.

  15. Systemic co-delivery of doxorubicin and siRNA using nanoparticles conjugated with EGFR-specific targeting peptide to enhance chemotherapy in ovarian tumor bearing mice

    Energy Technology Data Exchange (ETDEWEB)

    Liu, C. W.; Lin, W. J., E-mail: wjlin@ntu.edu.tw [National Taiwan University, Graduate Institute of Pharmaceutical Sciences, School of Pharmacy (China)

    2013-10-15

    This aim of this study was to develop peptide-conjugated nanoparticles (NPs) for systemic co-delivery of siRNA and doxorubicin to enhance chemotherapy in epidermal growth factor receptor (EGFR) high-expressed ovarian tumor bearing mice. The active targeting NPs were prepared using heptapeptide-conjugated poly(d,l-lactic-co-glycolic acid)-poly(ethylene glycol). The particle sizes of peptide-free and peptide-conjugated NPs were 159.3 {+-} 32.5 and 184.0 {+-} 52.9 nm, respectively, with zeta potential -21.3 {+-} 3.8 and -15.3 {+-} 2.8 mV. The peptide-conjugated NPs uptake were more efficient in EGFR high-expressed SKOV3 cells than in EGFR low-expressed HepG2 cells due to heptapeptide specificity. The NPs were used to deliver small molecule anticancer drug (e.g., doxorubicin) and large molecule genetic agent (e.g., siRNA). The IC{sub 50} of doxorubicin-loaded peptide-conjugated NPs (0.09 {+-} 0.06 {mu}M) was significantly lower than peptide-free NPs (5.72 {+-} 2.64 {mu}M). The similar result was observed in siRNA-loaded NPs. The peptide-conjugated NPs not only served as a nanocarrier to efficiently deliver doxorubicin and siRNA to EGFR high-expressed ovarian cancer cells but also increased the intracellular accumulation of the therapeutic agents to induce assured anti-tumor growth effect in vivo.

  16. Optical study of pi-conjugated polymers and pi-conjugated polymers/fullerene blends

    Science.gov (United States)

    Drori, Tomer

    In this research, we studied the optical properties of a variety of pi-conjugated polymers and pi-conjugated polymers/fullerene blends, using various continuous wave optical spectroscopies. We found an illumination-induced metastable polaron-supporting phase in films of a soluble derivative of poly-p-phenylene vinylene (MEH-PPV). Pristine, MEH-PPV polymer films in the dark do not show long-lived photogenerated polarons. Prolonged UV illumination, however, is found to induce a reversible, metastable phase characterized by its ability to support abundant long-lived photogenerated polarons. We also discovered a photobleaching band in our photomodulation measurement around 0.9eV that scales with and thus is related to the observed polaron band. In the dark, the illumination-induced metastable phase reverts back to the phase of the original MEH-PPV within about 30 min at room temperature. We also applied our experimental techniques in polymer/fullerene blends for studying the photophysics of bulk heterostructures with below-gap excitation. In contrast to the traditional view, we found that below-gap excitation, which is incapable of generating intrachain excitons, nevertheless efficiently generates polarons on the polymer chains and fullerene molecules. Using frequency dependence photomodulation, we distinguished between the two mechanisms of photoinduced charge transfer using above-gap and below-gap excitations, and found a distinguishable long polaron lifetime when photogenerated with below-gap excitation. The polaron action spectrum extends deep inside the gap as a result of a charge-transfer complex state formed between the polymer chain and fullerene molecule. Using the electroabsorption technique, we were able to detect the optical transition of the charge transfer complex state that lies below the gap of the polymer and the fullerene. With appropriate design engineering the long-lived polarons might be harvested in solar cell devices. Another system studied was

  17. Structure and Mode of Peptide Binding of Pheromone Receptor PrgZ

    NARCIS (Netherlands)

    Berntsson, Ronnie P. -A.; Schuurman-Wolters, Gea K.; Dunny, Gary; Slotboom, Dirk-Jan; Poolman, Bert

    2012-01-01

    Wepresent the crystal structure of the pheromone receptor protein PrgZ from Enterococcus faecalis in complex with the heptapeptide cCF10 (LVTLVFV), which is used in signaling between conjugative recipient and donor cells. Comparison of PrgZ with homologous oligopeptide-binding proteins (AppA and Opp

  18. Preparation of epidermal growth factor (EGF) conjugated iron oxide nanoparticles and their internalization into colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Creixell, Mar [Department of Chemical Engineering, University of Puerto Rico, Mayagueez Campus, P.O. Box 9000, Mayagueez, PR 00681 (Puerto Rico); Department of Electronics, Faculty of Physics, University of Barcelona, Av. Diagonal 647, 08028 Barcelona (Spain); Herrera, Adriana P.; Ayala, Vanessa; Latorre-Esteves, Magda [Department of Chemical Engineering, University of Puerto Rico, Mayagueez Campus, P.O. Box 9000, Mayagueez, PR 00681 (Puerto Rico); Perez-Torres, Marianela [Department of Pharmaceutical Sciences, University of Puerto Rico-Medical Sciences Campus, PO Box 365067, San Juan, PR 00936 (Puerto Rico); Torres-Lugo, Madeline [Department of Chemical Engineering, University of Puerto Rico, Mayagueez Campus, P.O. Box 9000, Mayagueez, PR 00681 (Puerto Rico); Rinaldi, Carlos, E-mail: carlos.rinaldi@upr.ed [Department of Chemical Engineering, University of Puerto Rico, Mayagueez Campus, P.O. Box 9000, Mayagueez, PR 00681 (Puerto Rico)

    2010-08-15

    Epidermal growth factor (EGF) was conjugated with carboxymethyldextran (CMDx) coated iron oxide magnetic nanoparticles using carbodiimide chemistry to obtain magnetic nanoparticles that target the epidermal growth factor receptor (EGFR). Epidermal growth factor modified magnetic nanoparticles were colloidally stable when suspended in biological buffers such as PBS and cell culture media. Both targeted and non-targeted nanoparticles were incubated with CaCo-2 cancer cells, known to overexpress EGFR. Nanoparticle localization within the cell was visualized by confocal laser scanning microscopy and light microscopy using Prussian blue stain. Results showed that targeted magnetic nanoparticles were rapidly accumulated in both flask-shaped small vesicles and large circular endocytic structures. Internalization patterns suggest that both clathrin-dependent and clathrin-independent receptors mediated endocytosis mechanisms are responsible for nanoparticle internalization.

  19. Preparation of epidermal growth factor (EGF) conjugated iron oxide nanoparticles and their internalization into colon cancer cells

    Science.gov (United States)

    Creixell, Mar; Herrera, Adriana P.; Ayala, Vanessa; Latorre-Esteves, Magda; Pérez-Torres, Marianela; Torres-Lugo, Madeline; Rinaldi, Carlos

    2010-08-01

    Epidermal growth factor (EGF) was conjugated with carboxymethyldextran (CMDx) coated iron oxide magnetic nanoparticles using carbodiimide chemistry to obtain magnetic nanoparticles that target the epidermal growth factor receptor (EGFR). Epidermal growth factor modified magnetic nanoparticles were colloidally stable when suspended in biological buffers such as PBS and cell culture media. Both targeted and non-targeted nanoparticles were incubated with CaCo-2 cancer cells, known to overexpress EGFR. Nanoparticle localization within the cell was visualized by confocal laser scanning microscopy and light microscopy using Prussian blue stain. Results showed that targeted magnetic nanoparticles were rapidly accumulated in both flask-shaped small vesicles and large circular endocytic structures. Internalization patterns suggest that both clathrin-dependent and clathrin-independent receptors mediated endocytosis mechanisms are responsible for nanoparticle internalization.

  20. New heparin–indomethacin conjugate with an ester linkage: Synthesis, self aggregation and drug delivery behavior

    Energy Technology Data Exchange (ETDEWEB)

    Li, Nan-Nan; Zheng, Bing-Na [DSAPM Lab and PCFM Lab, Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China); Lin, Jian-Tao [DSAPM Lab and PCFM Lab, Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China); Guangdong Medical College, Dongguan 523808 (China); Zhang, Li-Ming, E-mail: ceszhlm@mail.sysu.edu.cn [DSAPM Lab and PCFM Lab, Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China)

    2014-01-01

    New heparin–indomethacin conjugate with an ester linkage was prepared by the carbodiimide-mediated condensation reaction, and then characterized by FTIR and {sup 1}HNMR analyses. Due to its amphiphilic character, such a conjugate could self-aggregate into spherical nanoparticles in aqueous system, as confirmed by fluorescence spectroscopy, dynamic light scattering and transmission electron microscopy. By the in vitro drug release tests, the resultant conjugate nanoparticles were found to have a sustained and esterase-sensitive release behavior for conjugated indomethacin. In addition, the uptake of these conjugate nanoparticles into human nasopharyngeal carcinoma CNE1 cells was confirmed by fluorescence microscopy. - Highlights: • New heparin–indomethacin conjugate with an ester linkage was prepared. • Such a conjugate could self-aggregate into spherical nanoparticles in aqueous system. • The resultant conjugate nanoparticles exhibited an esterase-sensitive drug release behavior. • The resultant conjugate nanoparticles showed the cellular uptake ability in CNE1 cells.

  1. Conjugated agent insulin-antisense-c-myb-PS-ODN enhances the inhibitory effect on proliferation of rat aortic artery smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM:Vascular smooth muscle cell (SMC) proliferation and migration from the arterial wall media into the intima are believed to play a critical role in the pathogenesis of restenosis. Several studies have demonstrated that phosphothioate (PS) oligodeoxynucleotides targeted against genes involved in SMC proliferation inhibits in vitro SMC proliferation and migration. However, the therapeutic effect of antisense ODN on the individual who receives the treatment of delivery of the agent depends on the efficacy of this agent in great degree. We investigated the inhibition effect of a novel agent, insulin-antisense-c-myb-PS-ODN on SMC proliferation in vitro. METHODS:The rat aortic artery SMCs were cultured in Dulbecco's modified Eagel's medium. The passage 8 to 13 were used as the experiment. Cell surface receptor binding assay was quantified through counting gamma particles emitted from 125    I labeled insulin. SMC rapid proliferation was brought by stimulation of high concentration of fetal bovine serum (FBS). The novel agent of insulin conjugated to the antisense-c-myb-PS-ODN was obtained via incubation of both in condition of certain reagents, pH, temperature, and ion concentration. The characterization and purification of the agent was performed through HPLC. Inhibition of SMC proliferation was reflected by incorporation rate of trillium labeled thymidine deoxyribonucleotide.RESULTS:The binding efficacy of insulin to the receptor was remarkably increased in SMC cultured in supplement of 20% FBS. The inhibition effect of conjugator insulin-c-myb-antisense-PS-ODN was stronger than that of the simple c-myb-antisense-PS-ODN. The inhibition rate of conjugator and simple form on SMC proliferation were 48.34% and 29.54%, respectively. CONCLUSION:The binding efficacy and specificity of c-myb-antisense-PS-ODN to SMC may be enhanced by the insulin receptor mediation through the insulin-insulin receptor interaction. The insulin-receptor targeted method may be a

  2. Conjugated linoleic acid isomers and cancer.

    Science.gov (United States)

    Kelley, Nirvair S; Hubbard, Neil E; Erickson, Kent L

    2007-12-01

    We reviewed the literature regarding the effects of conjugated linoleic acid (CLA) preparations enriched in specific isomers, cis9, trans11-CLA (c9, t11-CLA) or trans10, cis12-CLA (t10, c12-CLA), on tumorigenesis in vivo and growth of tumor cell lines in vitro. We also examined the potential mechanisms by which CLA isomers may alter the incidence of cancer. We found no published reports that examined the effects of purified CLA isomers on human cancer in vivo. Incidence of rat mammary tumors induced by methylnitrosourea was decreased by c9, t11-CLA in all studies and by t10, c12-CLA in just a few that included it. Those 2 isomers decreased the incidence of forestomach tumors induced by benzo (a) pyrene in mice. Both isomers reduced breast and forestomach tumorigenesis. The c9, t11-CLA isomer did not affect the development of spontaneous tumors of the intestine or mammary gland, whereas t10, c12-CLA increased development of genetically induced mammary and intestinal tumors. In vitro, t10, c12-CLA inhibited the growth of mammary, colon, colorectal, gastric, prostate, and hepatoma cell lines. These 2 CLA isomers may regulate tumor growth through different mechanisms, because they have markedly different effects on lipid metabolism and regulation of oncogenes. In addition, c9, t11-CLA inhibited the cyclooxygenase-2 pathway and t10, c12-CLA inhibited the lipooxygenase pathway. The t10, c12-CLA isomer induced the expression of apoptotic genes, whereas c9, t11-CLA did not increase apoptosis in most of the studies that assessed it. Several minor isomers including t9, t11-CLA; c11, t13-CLA; c9, c11-CLA; and t7, c11-CLA were more effective than c9, t11-CLA or t10, c12-CLA in inhibiting cell growth in vitro. Additional studies with purified isomers are needed to establish the health benefit and risk ratios of each isomer in humans.

  3. The Preparation and Characterization of Conjugated Linolenic Acid

    Institute of Scientific and Technical Information of China (English)

    Cao Ying; Yang Lin; Chen Zhen-Yu

    2004-01-01

    Conjugated Linolenic Acid (CLN) has recently been shown to have a more strong cytotoxic effect on various human tumor cell lines than CLA. In CLN, all the three double bonds are conjugated, whereas they are methylene-interrupted in LN. Some seed oil, such as tung oil and pomegranate seed oil, principally consist of CLN, accounting for 76.5% and 75.5%, respectively.CLN can be characterized using the combination of gas chromatography (GC), highperformance liquid chromatography (HPLC) and UV /VIS spectrophotomea-ic analysis. GC can separate the CLN from other fatty acids and HPLC can separate the individual CLN isomers.The conjugated triene formation has a maximum absorbency at 268 nm and the conjugated diene formation has an absorbency at 235 nm in UV spectrum.CLN was prepared from linseed oil by isomerization reaction in our present study. By treating at was isomerized and the product was purified by recrystallizing in the methanol. The GC and UV /VIS spectrophotometric analysis were used to characterize the obtained products. It was found that the a-LN in the linseed oil was converted to the corresponding conjugated diene acids and CLN. The GC analysis also showed that there formed about 20% CLN when reacting for 10h with 40% KOH/ethylene glycol.

  4. Relaxation Oscillation with Picosecond Spikes in a Conjugated Polymer Laser

    Directory of Open Access Journals (Sweden)

    Wafa Musa Mujamammi

    2016-10-01

    Full Text Available Optically pumped conjugated polymer lasers are good competitors for dye lasers, often complementing and occasionally replacing them. This new type of laser material has broad bandwidths and high optical gains comparable to conventional laser dyes. Since the Stokes’ shift is unusually large, the conjugated polymer has a potential for high power laser action, facilitated by high concentration. This paper reports the results of a new conjugated polymer, the poly[(9,9-dioctyl-2,7-divinylenefluorenylene-alt-co-{2-methoxy-5-(2-ethylhexyloxy-1,4-phenylene}](PFO-co-MEH-PPV material, working in the green region. Also discussed are the spectral and temporal features of the amplified spontaneous emissions (ASE from the conjugated polymer PFO-co-MEH-PPV in a few solvents. When pumped by the third harmonic of the Nd:YAG laser of 10 ns pulse width, the time-resolved spectra of the ASE show relaxation oscillations and spikes of 600 ps pulses. To the best of our knowledge, this is the first report on relaxation oscillations in conjugated-polymer lasers.

  5. Social behavior and decision making in bacterial conjugation.

    Science.gov (United States)

    Koraimann, Günther; Wagner, Maria A

    2014-01-01

    Bacteria frequently acquire novel genes by horizontal gene transfer (HGT). HGT through the process of bacterial conjugation is highly efficient and depends on the presence of conjugative plasmids (CPs) or integrated conjugative elements (ICEs) that provide the necessary genes for DNA transmission. This review focuses on recent advancements in our understanding of ssDNA transfer systems and regulatory networks ensuring timely and spatially controlled DNA transfer (tra) gene expression. As will become obvious by comparing different systems, by default, tra genes are shut off in cells in which conjugative elements are present. Only when conditions are optimal, donor cells-through epigenetic alleviation of negatively acting roadblocks and direct stimulation of DNA transfer genes-become transfer competent. These transfer competent cells have developmentally transformed into specialized cells capable of secreting ssDNA via a T4S (type IV secretion) complex directly into recipient cells. Intriguingly, even under optimal conditions, only a fraction of the population undergoes this transition, a finding that indicates specialization and cooperative, social behavior. Thereby, at the population level, the metabolic burden and other negative consequences of tra gene expression are greatly reduced without compromising the ability to horizontally transfer genes to novel bacterial hosts. This undoubtedly intelligent strategy may explain why conjugative elements-CPs and ICEs-have been successfully kept in and evolved with bacteria to constitute a major driving force of bacterial evolution.

  6. Enzymatically catalyzed HES conjugation using microbial transglutaminase: Proof of feasibility.

    Science.gov (United States)

    Besheer, Ahmed; Hertel, Thomas C; Kressler, Jörg; Mäder, Karsten; Pietzsch, Markus

    2009-11-01

    Polymer-drug and polymer-protein conjugates are promising candidates for the delivery of therapeutic agents. PEGylation, using poly(ethylene glycol) for the conjugation, is now the gold standard in this field, and some PEGylated proteins have successfully reached the market. Hydroxyethyl starch (HES) is a water-soluble, biodegradable derivative of starch that is currently being investigated as a substitute for PEG. So far, only chemical methods have been suggested for HES conjugation; however, these may have detrimental effects on proteins. Here, we report an enzymatic method for HES conjugation using a recombinant microbial transglutaminase (rMTG). The latter catalyzes the acyl transfer between the gamma-carboxamide group of a glutaminyl residue (acyl donors) and a variety of primary amines (acyl acceptors), including the amino group of lysine. HES was modified with N-carbobenzyloxy glutaminyl glycine (Z-QG) and hexamethylene diamine (HMDA) to act as acyl donor and acyl acceptor, respectively. Using (1)H NMR, the degree of modification with Z-QG and HMDA was found to be 4.6 and 3.9 mol%, respectively. Using SDS-PAGE, it was possible to show that the modified HES successfully coupled to test compounds, proving that it is accepted as a substrate by rMTG. Finally, the process described in this study is a simple, mild approach to produce fully biodegradable polymer-drug and polymer-protein conjugates. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association

  7. Controlling molecular ordering in solution-state conjugated polymers.

    Science.gov (United States)

    Zhu, J; Han, Y; Kumar, R; He, Y; Hong, K; Bonnesen, P V; Sumpter, B G; Smith, S C; Smith, G S; Ivanov, I N; Do, C

    2015-10-01

    Rationally encoding molecular interactions that can control the assembly structure and functional expression in a solution of conjugated polymers hold great potential for enabling optimal organic optoelectronic and sensory materials. In this work, we show that thermally-controlled and surfactant-guided assembly of water-soluble conjugated polymers in aqueous solution is a simple and effective strategy to generate optoelectronic materials with the desired molecular ordering. We have studied a conjugated polymer consisting of a hydrophobic thiophene backbone and hydrophilic, thermo-responsive ethylene oxide side groups, which shows a step-wise, multi-dimensional assembly in water. By incorporating the polymer into phase-segregated domains of an amphiphilic surfactant in solution, we demonstrate that both chain conformation and degree of molecular ordering of the conjugated polymer can be tuned in hexagonal, micellar and lamellar phases of the surfactant solution. The controlled molecular ordering in conjugated polymer assembly is demonstrated as a key factor determining the electronic interaction and optical function.

  8. Polymer-cysteamine conjugates: new mucoadhesive excipients for drug delivery?

    Science.gov (United States)

    Kast, Constantia E; Bernkop-Schnürch, Andreas

    2002-03-02

    In the present study, the features of two new thiolated polymers--the so-called thiomers--were investigated. Mediated by a carbodiimide cysteamine was covalently attached to sodium carboxymethylcellulose (Na-CMC) and neutralised polycarbophil (Na-PCP). Depending on the weight-ratio polymer to cysteamine during the coupling reaction, the resulting CMC-cysteamine conjugate and PCP-cysteamine conjugate showed in maximum 43 +/- 15 and 138 +/- 22 micromole thiol groups per g polymer (mean +/- S.D.; n=3), respectively, which were used for further characterisation. Tensile studies carried out with the CMC-cysteamine conjugate on freshly excised porcine intestinal mucosa displayed no significantly (Paqueous solutions the disintegration time of tablets based on the CMC- and PCP-cysteamine conjugates was prolonged 1.5 and 3.2-fold, respectively, in comparison to tablets containing the corresponding unmodified polymers. According to these results, especially the PCP-cysteamine conjugate represents a promising new pharmaceutical excipient for various drug delivery systems.

  9. A Comparative Study of Two Folate-Conjugated Gold Nanoparticles for Cancer Nanotechnology Applications

    Directory of Open Access Journals (Sweden)

    Ali Shakeri-Zadeh

    2010-11-01

    Full Text Available We report a comparative study of synthesis, characteristics and in vitro tests of two folate-conjugated gold nanoparticles (AuNP differing in linkers and AuNP sizes for selective targeting of folate-receptor positive cancerous cells. The linkers chosen were 4-aminothiophenol (4Atp and 6-mercapto-1-hexanol (MH with nanoconjugate products named Folate-4Atp-AuNP and Folate-MH-AuNP. We report the folate-receptor tissue distribution and its endocytosis for targeted nanotechnology. Comparison of the two nanoconjugates’ syntheses and characterization is also reported, including materials and methods of synthesis, UV-visible absorption spectroscopic measurements, Fourier Transform Infra Red (FTIR measurements, Transmission electron microscopy (TEM images and size distributions, X-ray diffraction data, elemental analyses and chemical stability comparison. In addition to the analytical characterization of the nanoconjugates, the cell lethality was measured in HeLa (high level of folate receptor expression and MCF-7 (low level of folate receptor expression cells. The nanoconjugates themselves, as well as the intense pulsed light (IPL were not harmful to cell viability. However, upon stimulation of the folate targeted nanoconjugates with the IPL, ~98% cell killing was found in HeLa cells and only ~9% in MCF-7 cells after four hours incubation with the nanoconjugate. This demonstrates that folate targeting is effective in selecting for specific cell populations. Considering the various comparisons made, we conclude that Folate-4Atp-AuNP is superior to Folate-MH-AuNP for cancer therapy.

  10. Novel conjugates of peptides and conjugated polymers for optoelectronics and neural interfaces

    Science.gov (United States)

    Bhagwat, Nandita

    Peptide-polymer conjugates are a novel class of hybrid materials that take advantage of each individual component giving the opportunity to generate materials with unique physical, chemical, mechanical, optical, and electronic properties. In this dissertation peptide-polymer conjugates for two different applications are discussed. The first set of peptide-polymer conjugates were developed as templates to study the intermolecular interactions between electroactive molecules by manipulating the intermolecular distances at nano-scale level. A PEGylated, alpha-helical peptide template was employed to effectively display an array of organic chromophores (oxadiazole containing phenylenevinylene oligomers, Oxa-PPV). Three Oxa-PPV chromophores were strategically positioned on each template, at distances ranging from 6 to 17 A from each other, as dictated by the chemical and structural properties of the peptide. The Oxa-PPV modified PEGylated helical peptides (produced via Heck coupling strategies) were characterized by a variety of spectroscopic methods. Electronic contributions from multiple pairs of chromophores on a scaffold were detectable; the number and relative positioning of the chromophores dictated the absorbance and emission maxima, thus confirming the utility of these polymer--peptide templates for complex presentation of organic chromophores. The rest of the thesis is focused on using poly(3,4-alkylenedioxythiophene) based conjugated polymers as coatings for neural electrodes. This thiophene derivative is of considerable current interest for functionalizing the surfaces of a wide variety of devices including implantable biomedical electronics, specifically neural bio-electrodes. Toward these ends, copolymer films of 3,4-ethylenedioxythiophene (EDOT) with a carboxylic acid functional EDOT (EDOTacid) were electrochemically deposited and characterized as a systematic function of the EDOTacid content (0, 25, 50, 75, and 100%). The chemical surface characterization

  11. Relationships of circulating pregnanolone isomers and their polar conjugates to the status of sex, menstrual cycle, and pregnancy.

    Science.gov (United States)

    Kancheva, Radmila; Hill, Martin; Cibula, David; Vceláková, Helena; Kancheva, Lyudmila; Vrbíková, Jana; Fait, Tomás; Parízek, Antonín; Stárka, Luboslav

    2007-10-01

    Pregnanolone isomers (PIs) and their polar conjugates (PICs) modulate ionotropic receptors such as gamma-aminobutyric acid or pregnane X receptors. Besides, brain synthesis, PI penetrates the blood-brain barrier. We evaluated the physiological importance of PI respecting the status of sex, menstrual cycle, and pregnancy. Accordingly, circulating levels of allopregnanolone (P3alpha 5alpha ), isopregnanolone (P3beta 5alpha ), pregnanolone (P3alpha 5beta ), epipregnanolone (P3beta 5beta ), their polar conjugates, and related steroids were measured in 15 men (M), 15 women in the follicular phase (F), 16 women in the luteal phase (L), and 30 women in the 36th week of gestation (P) using GC-MS. The steroid levels were similar in M and F, increased about thrice in L and escalated in P (38-410 times compared with F). The PICs were prevalent over the PIs (16-150 times). Higher ratios of 5alpha-PIC to 5alpha-PI found in P indicate the more intensive conjugation of 5alpha-PI during pregnancy. This mechanism probably provides for the elimination of neuroinhibitory P3alpha 5alpha in the maternal compartment. Additionally, our result points to a limited sulfation capacity for neuroinhibitory P3alpha 5beta in P. In contrast to the situation in M, F, and L where the P3alpha 5beta C is the most abundant PIC, and P3alpha 5beta is present in minor quantities compared with the P3alpha 5alpha, P3alpha 5beta may acquire physiological importance during pregnancy, contributing to the sustaining thereof. On the other hand, the declining formation of P3alpha 5beta may participate in the initiation of parturition, given the relative abundance of the steroid, its potency to suppress the activity of oxytocin-producing cells and its effectiveness in uterine relaxation.

  12. Conjugating folate on superparamagnetic Fe{sub 3}O{sub 4}@Au nanoparticles using click chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Xiaofang, E-mail: xfshen@jiangnan.edu.cn; Ge, Zhaoqiang; Pang, Yuehong

    2015-02-15

    Gold-coated magnetic core@shell nanoparticles, which exhibit magneto-optical properties, not only enhance the chemical stability of core and biocompatibility of surface, but also provide a combination of multimodal imaging and therapeutics. The conjugation of these tiny nanoparticles with specific biomolecules allows researchers to target the desired location. In this paper, superparamagnetic Fe{sub 3}O{sub 4}@Au nanoparticles were synthesized and functionalized with the azide group on the surface by formation of self-assembled monolayers. Folate (FA) molecules, non-immunogenic target ligands for cancer cells, are conjugated with alkyne and then immobilized on the azide-terminated Fe{sub 3}O{sub 4}@Au nanoparticles through copper(I)-catalyzed azide-alkyne cycloaddition (click reaction). Myelogenous leukemia K562 cells were used as a folate receptor (FR) model, which can be targeted and extracted by magnetic field after interaction with the Fe{sub 3}O{sub 4}@Au–FA nanoparticles. - Graphical abstract: Self-assembled azide-terminated group on superparamagnetic Fe{sub 3}O{sub 4}@Au nanoparticles followed by click reaction with alkyne-functionalized folate, allowing the nanoparticles target folate receptor of cancer cells. - Highlights: • Azidoundecanethiol was coated on the superparamagnetic Fe{sub 3}O{sub 4}@Au nanoparticles by forming self-assembled monolayers. • Alkyne-terminated folate was synthesized from a reaction between the amine and the carboxylic acid. • Conjugation of Fe{sub 3}O{sub 4}@Au nanoparticles with folate was made by copper-catalyzed azide-alkyne cycloaddition click chemistry.

  13. The use of radiocobalt as a label improves imaging of EGFR using DOTA-conjugated Affibody molecule

    DEFF Research Database (Denmark)

    Garousi, Javad; Andersson, Ken G; Dam, Johan H

    2017-01-01

    Several anti-cancer therapies target the epidermal growth factor receptor (EGFR). Radionuclide imaging of EGFR expression in tumours may aid in selection of optimal cancer therapy. The (111)In-labelled DOTA-conjugated ZEGFR:2377 Affibody molecule was successfully used for imaging of EGFR-expressi......Several anti-cancer therapies target the epidermal growth factor receptor (EGFR). Radionuclide imaging of EGFR expression in tumours may aid in selection of optimal cancer therapy. The (111)In-labelled DOTA-conjugated ZEGFR:2377 Affibody molecule was successfully used for imaging of EGFR......-expressing xenografts in mice. An optimal combination of radionuclide, chelator and targeting protein may further improve the contrast of radionuclide imaging. The aim of this study was to evaluate the targeting properties of radiocobalt-labelled DOTA-ZEGFR:2377. DOTA-ZEGFR:2377 was labelled with (57)Co (T1/2 = 271.8 d......-DOTA-ZEGFR:2377 demonstrated EGFR-specific accumulation in A431 xenografts and EGFR-expressing tissues in mice. Tumour-to-organ ratios for the radiocobalt-labelled DOTA-ZEGFR:2377 were significantly higher than for the gallium-labelled counterpart already at 3 h after injection. Importantly, (57)Co...

  14. Thin Films Formed from Conjugated Polymers with Ionic, Water-Soluble Backbones.

    Science.gov (United States)

    Voortman, Thomas P; Chiechi, Ryan C

    2015-12-30

    This paper compares the morphologies of films of conjugated polymers in which the backbone (main chain) and pendant groups are varied between ionic/hydrophilic and aliphatic/hydrophobic. We observe that conjugated polymers in which the pendant groups and backbone are matched, either ionic-ionic or hydrophobic-hydrophobic, form smooth, structured, homogeneous films from water (ionic) or tetrahydrofuran (hydrophobic). Mismatched conjugated polymers, by contrast, form inhomogeneous films with rough topologies. The polymers with ionic backbone chains are conjugated polyions (conjugated polymers with closed-shell charges in the backbone), which are semiconducting materials with tunable bad-gaps, not unlike uncharged conjugated polymers.

  15. Chemically optimized antimyosin Fab conjugates with chelating polymers: importance of the nature of the protein-polymer single site covalent bond for biodistribution and infarction localization.

    Science.gov (United States)

    Trubetskoy, V S; Narula, J; Khaw, B A; Torchilin, V P

    1993-01-01

    Murine antimyosin Fab fragment was conjugated with 111In-labeled N-terminal-modified DTPA-polylysine using three bifunctional reagents: N-hydroxysuccinimide esters of 3-(2-pyridyldithio)propionic acid (SPDP conjugate), 4-(maleimidomethyl)cyclohexanecarboxylic acid (SMCC conjugate) and bromoacetic acid (BrAc conjugate) for potential localization of experimental myocardial infarction. Using various antibody preparations and a rabbit acute myocardial infarction model the following parameters were observed: (1) an in vitro antigen binding activity of SPDP conjugate = SMCC conjugate > BrAc conjugate, (2) a blood clearance rate of SPDP conjugate > BrAc conjugate > SMCC conjugate, (3) a liver and splenic accumulation of SPDP conjugate > BrAc conjugate > SMCC conjugate, and (4) the infarcted tissue activity showed an accumulation of SMCC conjugate > SPDP conjugate > BrAc conjugate. This study exemplifies the importance of rational chemical design of antimyosin Fab-chelating polymer conjugate for improved target tissue localization in vivo.

  16. Synthesis and Spectral Studies of CdTe–Dendrimer Conjugates

    Directory of Open Access Journals (Sweden)

    Ghosh Srabanti

    2009-01-01

    Full Text Available Abstract In order to couple high cellular uptake and target specificity of dendrimer molecule with excellent optical properties of semiconductor nanoparticles, the interaction of cysteine-capped CdTe quantum dots with dendrimer was investigated through spectroscopic techniques. NH2-terminated dendrimer molecule quenched the photoluminescence of CdTe quantum dots. The binding constants and binding capacity were calculated, and the nature of binding was found to be noncovalent. Significant decrease in luminescence intensity of CdTe quantum dots owing to noncovalent binding with dendrimer limits further utilization of these nanoassemblies. Hence, an attempt is made, for the first time, to synthesize stable, highly luminescent, covalently linked CdTe–Dendrimer conjugate in aqueous medium using glutaric dialdehyde (G linker. Conjugate has been characterized through Fourier transform infrared spectroscopy and transmission electron microscopy. In this strategy, photoluminescence quantum efficiency of CdTe quantum dots with narrow emission bandwidths remained unaffected after formation of the conjugate.

  17. Synthesis and Spectral Studies of CdTe-Dendrimer Conjugates

    Science.gov (United States)

    Ghosh, Srabanti; Saha, Abhijit

    2009-08-01

    In order to couple high cellular uptake and target specificity of dendrimer molecule with excellent optical properties of semiconductor nanoparticles, the interaction of cysteine-capped CdTe quantum dots with dendrimer was investigated through spectroscopic techniques. NH2-terminated dendrimer molecule quenched the photoluminescence of CdTe quantum dots. The binding constants and binding capacity were calculated, and the nature of binding was found to be noncovalent. Significant decrease in luminescence intensity of CdTe quantum dots owing to noncovalent binding with dendrimer limits further utilization of these nanoassemblies. Hence, an attempt is made, for the first time, to synthesize stable, highly luminescent, covalently linked CdTe-Dendrimer conjugate in aqueous medium using glutaric dialdehyde (G) linker. Conjugate has been characterized through Fourier transform infrared spectroscopy and transmission electron microscopy. In this strategy, photoluminescence quantum efficiency of CdTe quantum dots with narrow emission bandwidths remained unaffected after formation of the conjugate.

  18. Recent advances in the construction of antibody-drug conjugates

    Science.gov (United States)

    Chudasama, Vijay; Maruani, Antoine; Caddick, Stephen

    2016-02-01

    Antibody-drug conjugates (ADCs) comprise antibodies covalently attached to highly potent drugs using a variety of conjugation technologies. As therapeutics, they combine the exquisite specificity of antibodies, enabling discrimination between healthy and diseased tissue, with the cell-killing ability of cytotoxic drugs. This powerful and exciting class of targeted therapy has shown considerable promise in the treatment of various cancers with two US Food and Drug Administration approved ADCs currently on the market (Adcetris and Kadcyla) and approximately 40 currently undergoing clinical evaluation. However, most of these ADCs exist as heterogeneous mixtures, which can result in a narrow therapeutic window and have major pharmacokinetic implications. In order for ADCs to deliver their full potential, sophisticated site-specific conjugation technologies to connect the drug to the antibody are vital. This Perspective discusses the strategies currently used for the site-specific construction of ADCs and appraises their merits and disadvantages.

  19. Repercussions of imprisonment for conjugal violence: discourses of men

    Directory of Open Access Journals (Sweden)

    Anderson Reis de Sousa

    Full Text Available ABSTRACT Objective: to know the consequences that men experience related to incarceration by conjugal violence. Methods: qualitative study on 20 men in jail and indicted in criminal processes related to conjugal violence in a Court specialized in Family and Domestic Violence against women. The interviews were classified based on Collective Subject Discourse method, using NVIVO(r software. Results: the collective discourse shows that the experience of preventive imprisonment starts a process of family dismantling, social stigma, financial hardship and psycho-emotional symptoms such as phobia, depression, hypertension, and headaches. Conclusion: due to the physical, mental and social consequences of the conjugal violence-related imprisonment experience, it is urgent to look carefully into the somatization process as well as to the prevention strategies regarding this process.

  20. Progress towards meningitis prevention in the conjugate vaccines era

    Directory of Open Access Journals (Sweden)

    Cristina Aparecida Borges Laval

    2003-10-01

    Full Text Available Acute bacterial meningitis is an important cause of morbidity and mortality among children less than five years old. Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis are the most important agents of bacterial meningitis in developing countries. The development of the conjugate vaccines in the beginning of the 90's, especially type b H. influenzae (Hib, and more recently the heptavalent pneumococcal and the serogroup C meningococcal vaccines, have contributed directly to changes in the epidemiological profile of these invasive diseases (direct effect and of their carriage status (indirect effect. We review the impact of the Hib conjugate vaccine in Latin American countries, where this vaccine has been implemented, and the potential of pneumococcal and meningococcal conjugate vaccines for the reduction of meningitis worldwide. We also address constraints for the development and delivery of these vaccines and review new candidate state-of-the-art vaccines. The greatest challenge, undoubtedly, is to implement these vaccines worldwide, especially in the developing regions.

  1. Conjugates of a photoactivated rhodamine with biopolymers for cell staining.

    Science.gov (United States)

    Zaitsev, Sergei Yu; Shaposhnikov, Mikhail N; Solovyeva, Daria O; Solovyeva, Valeria V; Rizvanov, Albert A

    2014-01-01

    Conjugates of the photoactivated rhodamine dyes with biopolymers (proteins, polysaccharides, and nucleic acids) are important tools for microscopic investigation of biological tissue. In this study, a precursor of the photoactivated fluorescent dye (PFD) has been successfully used for staining of numerous mammalian cells lines and for conjugate formation with chitosan ("Chitosan-PFD") and histone H1 ("Histone H1.3-PFD"). The intensive fluorescence has been observed after photoactivation of these conjugates inside cells (A431, HaCaT, HEK239, HBL-100, and MDCK). Developed procedures and obtained data are important for further application of novel precursors of fluorescent dyes ("caged" dyes) for microscopic probing of biological objects. Thus, the synthesized "Chitosan-PFD" and "Histone H1-PFD" have been successfully applied in this study for intracellular transport visualization by fluorescent microscopy.

  2. Nano-assembly of nanodiamonds by conjugation to actin filaments.

    Science.gov (United States)

    Bradac, Carlo; Say, Jana M; Rastogi, Ishan D; Cordina, Nicole M; Volz, Thomas; Brown, Louise J

    2016-03-01

    Fluorescent nanodiamonds (NDs) are remarkable objects. They possess unique mechanical and optical properties combined with high surface areas and controllable surface reactivity. They are non-toxic and hence suited for use in biological environments. NDs are also readily available and commercially inexpensive. Here, the exceptional capability of controlling and tailoring their surface chemistry is demonstrated. Small, bright diamond nanocrystals (size ˜30 nm) are conjugated to protein filaments of actin (length ˜3-7 µm). The conjugation to actin filaments is extremely selective and highly target-specific. These unique features, together with the relative simplicity of the conjugation-targeting method, make functionalised nanodiamonds a powerful and versatile platform in biomedicine and quantum nanotechnologies. Applications ranging from using NDs as superior biological markers to, potentially, developing novel bottom-up approaches for the fabrication of hybrid quantum devices that would bridge across the bio/solid-state interface are presented and discussed.

  3. New Approaches to Conjugated Polymer Electrodes for Organic Energy Storage

    Science.gov (United States)

    Lutkenhaus, Jodie

    2013-03-01

    Conjugated polymers have been explored as electrodes in batteries and pseudocapacitors for over 30 years. Yet, their widespread implementation has been hindered for several reasons such as oxidative stability, low capacity, and rate limitations associated with ionic mobility relative to current state-of-the-art. On the other hand, conjugated polymers have much to offer because of their good electronic conductivity, high Coulombic efficiency, and theoretical capacities comparable to those of metal oxides. Our lab's current goal is to overcome the aforementioned challenges, so that conjugated polymeric electrodes can be suitable used in energy storage for applications such as mechanically flexible energy storage and structural power system. This talk will present several approaches towards synthesis and processing of polyaniline that achieve oxidatively stable, high capacity, ionically mobile electrodes. These approaches include template polymerization, synthesis of nanofibers, and layer-by-layer assembly.

  4. Repercussions of imprisonment for conjugal violence: discourses of men 1

    Science.gov (United States)

    de Sousa, Anderson Reis; Pereira, Álvaro; Paixão, Gilvânia Patrícia do Nascimento; Pereira, Nadirlene Gomes; Campos, Luana Moura; Couto, Telmara Menezes

    2016-01-01

    ABSTRACT Objective: to know the consequences that men experience related to incarceration by conjugal violence. Methods: qualitative study on 20 men in jail and indicted in criminal processes related to conjugal violence in a Court specialized in Family and Domestic Violence against women. The interviews were classified based on Collective Subject Discourse method, using NVIVO(r) software. Results: the collective discourse shows that the experience of preventive imprisonment starts a process of family dismantling, social stigma, financial hardship and psycho-emotional symptoms such as phobia, depression, hypertension, and headaches. Conclusion: due to the physical, mental and social consequences of the conjugal violence-related imprisonment experience, it is urgent to look carefully into the somatization process as well as to the prevention strategies regarding this process. PMID:27982312

  5. Full Eulerian lattice Boltzmann model for conjugate heat transfer.

    Science.gov (United States)

    Hu, Yang; Li, Decai; Shu, Shi; Niu, Xiaodong

    2015-12-01

    In this paper a full Eulerian lattice Boltzmann model is proposed for conjugate heat transfer. A unified governing equation with a source term for the temperature field is derived. By introducing the source term, we prove that the continuity of temperature and its normal flux at the interface is satisfied automatically. The curved interface is assumed to be zigzag lines. All physical quantities are recorded and updated on a Cartesian grid. As a result, any complicated treatment near the interface is avoided, which makes the proposed model suitable to simulate the conjugate heat transfer with complex interfaces efficiently. The present conjugate interface treatment is validated by several steady and unsteady numerical tests, including pure heat conduction, forced convection, and natural convection problems. Both flat and curved interfaces are also involved. The obtained results show good agreement with the analytical and/or finite volume results.

  6. Progress towards meningitis prevention in the conjugate vaccines era

    Directory of Open Access Journals (Sweden)

    Cristina Aparecida Borges Laval

    Full Text Available Acute bacterial meningitis is an important cause of morbidity and mortality among children less than five years old. Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis are the most important agents of bacterial meningitis in developing countries. The development of the conjugate vaccines in the beginning of the 90's, especially type b H. influenzae (Hib, and more recently the heptavalent pneumococcal and the serogroup C meningococcal vaccines, have contributed directly to changes in the epidemiological profile of these invasive diseases (direct effect and of their carriage status (indirect effect. We review the impact of the Hib conjugate vaccine in Latin American countries, where this vaccine has been implemented, and the potential of pneumococcal and meningococcal conjugate vaccines for the reduction of meningitis worldwide. We also address constraints for the development and delivery of these vaccines and review new candidate state-of-the-art vaccines. The greatest challenge, undoubtedly, is to implement these vaccines worldwide, especially in the developing regions.

  7. Conjugates of a Photoactivated Rhodamine with Biopolymers for Cell Staining

    Science.gov (United States)

    Zaitsev, Sergei Yu.; Shaposhnikov, Mikhail N.; Solovyeva, Daria O.; Solovyeva, Valeria V.; Rizvanov, Albert A.

    2014-01-01

    Conjugates of the photoactivated rhodamine dyes with biopolymers (proteins, polysaccharides, and nucleic acids) are important tools for microscopic investigation of biological tissue. In this study, a precursor of the photoactivated fluorescent dye (PFD) has been successfully used for staining of numerous mammalian cells lines and for conjugate formation with chitosan (“Chitosan-PFD”) and histone H1 (“Histone H1.3-PFD”). The intensive fluorescence has been observed after photoactivation of these conjugates inside cells (A431, HaCaT, HEK239, HBL-100, and MDCK). Developed procedures and obtained data are important for further application of novel precursors of fluorescent dyes (“caged” dyes) for microscopic probing of biological objects. Thus, the synthesized “Chitosan-PFD” and “Histone H1-PFD” have been successfully applied in this study for intracellular transport visualization by fluorescent microscopy. PMID:25383365

  8. A DIRECT SEARCH FRAME-BASED CONJUGATE GRADIENTS METHOD

    Institute of Scientific and Technical Information of China (English)

    I.D. Coope; C.J. Price

    2004-01-01

    A derivative-free frame-based conjugate gradients algorithm is presented. Convergence is shown for C1 functions, and this is verified in numerical trials. The algorithm is tested on a variety of low dimensional problems, some of which are ill-conditioned, and is also tested on problems of high dimension. Numerical results show that the algorithm is effective on both classes of problems. The results are compared with those from a discrete quasiNewton method, showing that the conjugate gradients algorithm is competitive. The algorithm exhibits the conjugate gradients speed-up on problems for which the Hessian at the solution has repeated or clustered eigenvalues. The algorithm is easily parallelizable.

  9. Conjugates of a Photoactivated Rhodamine with Biopolymers for Cell Staining

    Directory of Open Access Journals (Sweden)

    Sergei Yu. Zaitsev

    2014-01-01

    Full Text Available Conjugates of the photoactivated rhodamine dyes with biopolymers (proteins, polysaccharides, and nucleic acids are important tools for microscopic investigation of biological tissue. In this study, a precursor of the photoactivated fluorescent dye (PFD has been successfully used for staining of numerous mammalian cells lines and for conjugate formation with chitosan (“Chitosan-PFD” and histone H1 (“Histone H1.3-PFD”. The intensive fluorescence has been observed after photoactivation of these conjugates inside cells (A431, HaCaT, HEK239, HBL-100, and MDCK. Developed procedures and obtained data are important for further application of novel precursors of fluorescent dyes (“caged” dyes for microscopic probing of biological objects. Thus, the synthesized “Chitosan-PFD” and “Histone H1-PFD” have been successfully applied in this study for intracellular transport visualization by fluorescent microscopy.

  10. Principles of conjugating quantum dots to proteins via carbodiimide chemistry.

    Science.gov (United States)

    Song, Fayi; Chan, Warren C W

    2011-12-09

    The covalent coupling of nanomaterials to bio-recognition molecules is a critical intermediate step in using nanomaterials for biology and medicine. Here we investigate the carbodiimide-mediated conjugation of fluorescent quantum dots to different proteins (e.g., immunoglobulin G, bovine serum albumin, and horseradish peroxidase). To enable these studies, we developed a simple method to isolate quantum dot bioconjugates from unconjugated quantum dots. The results show that the reactant concentrations and protein type will impact the overall number of proteins conjugated onto the surfaces of the quantum dots, homogeneity of the protein-quantum dot conjugate population, quantum efficiency, binding avidity, and enzymatic kinetics. We propose general principles that should be followed for the successful coupling of proteins to quantum dots.

  11. Preparation of conjugated polymer suspensions by using ultrasonic atomizer

    Energy Technology Data Exchange (ETDEWEB)

    Tada, Kazuya, E-mail: tada@eng.u-hyogo.ac.jp; Onoda, Mitsuyoshi

    2010-11-30

    The electrophoretic deposition is a method useful to prepare conjugated polymer films for electronic devices. This method provides high material recovery rate on the substrate from the suspension, in contrast to the conventional spin-coating in which most of the material placed on the substrate is blown away. Although manual reprecipitation technique successfully yields suspensions of various conjugated polymers including polyfluorene derivatives, it is favorable to control the preparation process of suspensions. In this context, this paper reports preliminary results on the preparation of suspension of conjugated polymer by using an ultrasonic atomizer. While the resultant films do not show particular difference due to the preparation methods of the suspension, the electric current profiles during the electrophoretic deposition suggests that the ultrasonic atomization of polymer solution prior to be mixed with poor solvent results in smaller and less uniform colloidal particles than the conventional manual pouring method.

  12. Streamline upwind finite element method for conjugate heat transfer problems

    Institute of Scientific and Technical Information of China (English)

    Niphon Wansophark; Atipong Malatip; Pramote Dechaumphai; Yunming Chen

    2005-01-01

    This paper presents a combined finite element method for solving conjugate heat transfer problems where heat conduction in a solid is coupled with heat convection in viscous fluid flow. The streamline upwind finite element method is used for the analysis of thermal viscous flow in the fluid region, whereas the analysis of heat conduction in solid region is performed by the Galerkin method. The method uses the three-node triangular element with equal-order interpolation functions for all the variables of the velocity components,the pressure and the temperature. The main advantage of the proposed method is to consistently couple heat transfer along the fluid-solid interface. Three test cases, i.e. conjugate Couette flow problem in parallel plate channel, counter-flow in heat exchanger, and conjugate natural convection in a square cavity with a conducting wall, are selected to evaluate the efficiency of the present method.

  13. Novel antibody-antibiotic conjugate eliminates intracellular S. aureus.

    Science.gov (United States)

    Lehar, Sophie M; Pillow, Thomas; Xu, Min; Staben, Leanna; Kajihara, Kimberly K; Vandlen, Richard; DePalatis, Laura; Raab, Helga; Hazenbos, Wouter L; Morisaki, J Hiroshi; Kim, Janice; Park, Summer; Darwish, Martine; Lee, Byoung-Chul; Hernandez, Hilda; Loyet, Kelly M; Lupardus, Patrick; Fong, Rina; Yan, Donghong; Chalouni, Cecile; Luis, Elizabeth; Khalfin, Yana; Plise, Emile; Cheong, Jonathan; Lyssikatos, Joseph P; Strandh, Magnus; Koefoed, Klaus; Andersen, Peter S; Flygare, John A; Wah Tan, Man; Brown, Eric J; Mariathasan, Sanjeev

    2015-11-19

    Staphylococcus aureus is considered to be an extracellular pathogen. However, survival of S. aureus within host cells may provide a reservoir relatively protected from antibiotics, thus enabling long-term colonization of the host and explaining clinical failures and relapses after antibiotic therapy. Here we confirm that intracellular reservoirs of S. aureus in mice comprise a virulent subset of bacteria that can establish infection even in the presence of vancomycin, and we introduce a novel therapeutic that effectively kills intracellular S. aureus. This antibody-antibiotic conjugate consists of an anti-S. aureus antibody conjugated to a highly efficacious antibiotic that is activated only after it is released in the proteolytic environment of the phagolysosome. The antibody-antibiotic conjugate is superior to vancomycin for treatment of bacteraemia and provides direct evidence that intracellular S. aureus represents an important component of invasive infections.

  14. Conjugated bilirubin in neonates with glucose-6-phosphate dehydrogenase deficiency.

    Science.gov (United States)

    Kaplan, M; Rubaltelli, F F; Hammerman, C; Vilei, M T; Leiter, C; Abramov, A; Muraca, M

    1996-05-01

    We used a system capable of measuring conjugated bilirubin and its monoconjugated and diconjugated fractions in serum to assess bilirubin conjugation in 29 glucose-6-phosphate dehydrogenase (G6PD)-deficient, term, male newborn infants and 35 control subjects; all had serum bilirubin levels > or = 256 mumol/L (15 mg/dI). The median value for diconjugated bilirubin was lower in the G6PD-deficient neonates than in control subjects (0.06 (range 0.00 to 1.84) vs 0.21 (range 0.00 to 1.02) mumol/L, p = 0.006). Diglucuronide was undetectable in 11 (38.9%) of the G6PD-deficient infants versus 3 (8.6%) of the control subjects (p = 0.015). These findings imply a partial defect of bilirubin conjugation not previously demonstrated in G6PD-deficient newborn infants.

  15. Microscopic and spectroscopic analysis of chitosan-DNA conjugates.

    Science.gov (United States)

    Agudelo, D; Kreplak, L; Tajmir-Riahi, H A

    2016-02-10

    Conjugations of DNA with chitosans 15 kD (ch-15), 100 kD (ch-100) and 200 kD (ch-200) were investigated in aqueous solution at pH 5.5-6.5. Multiple spectroscopic methods and atomic force microscopy (AFM) were used to locate the chitosan binding sites and the effect of polymer conjugation on DNA compaction and particle formation. Structural analysis showed that chitosan-DNA conjugation is mainly via electrostatic interactions through polymer cationic charged NH2 and negatively charged backbone phosphate groups. As polymer size increases major DNA compaction and particle formation occurs. At high chitosan concentration major DNA structural changes observed indicating a partial B to A-DNA conformational transition.

  16. The extended regulatory networks of SXT/R391 integrative and conjugative elements and IncA/C conjugative plasmids.

    Science.gov (United States)

    Poulin-Laprade, Dominic; Carraro, Nicolas; Burrus, Vincent

    2015-01-01

    Nowadays, healthcare systems are challenged by a major worldwide drug resistance crisis caused by the massive and rapid dissemination of antibiotic resistance genes and associated emergence of multidrug resistant pathogenic bacteria, in both clinical and environmental settings. Conjugation is the main driving force of gene transfer among microorganisms. This mechanism of horizontal gene transfer mediates the translocation of large DNA fragments between two bacterial cells in direct contact. Integrative and conjugative elements (ICEs) of the SXT/R391 family (SRIs) and IncA/C conjugative plasmids (ACPs) are responsible for the dissemination of a broad spectrum of antibiotic resistance genes among diverse species of Enterobacteriaceae and Vibrionaceae. The biology, diversity, prevalence and distribution of these two families of conjugative elements have been the subject of extensive studies for the past 15 years. Recently, the transcriptional regulators that govern their dissemination through the expression of ICE- or plasmid-encoded transfer genes have been described. Unrelated repressors control the activation of conjugation by preventing the expression of two related master activator complexes in both types of elements, i.e., SetCD in SXT/R391 ICEs and AcaCD in IncA/C plasmids. Finally, in addition to activating ICE- or plasmid-borne genes, these master activators have been shown to specifically activate phylogenetically unrelated mobilizable genomic islands (MGIs) that also disseminate antibiotic resistance genes and other adaptive traits among a plethora of pathogens such as Vibrio cholerae and Salmonella enterica.

  17. Push-pull macrocycles: donor-acceptor compounds with paired linearly conjugated or cross-conjugated pathways.

    Science.gov (United States)

    Leu, Wade C W; Fritz, Amanda E; Digianantonio, Katherine M; Hartley, C Scott

    2012-03-01

    Two-dimensional π-systems are of current interest in the design of functional organic molecules, exhibiting unique behavior for applications in organic electronics, single-molecule devices, and sensing. Here we describe the synthesis and characterization of "push-pull macrocycles": electron-rich and electron-poor moieties linked by a pair of (matched) conjugated bridges. We have developed a two-component macrocyclization strategy that allows these structures to be synthesized with efficiencies comparable to acyclic donor-bridge-acceptor systems. Compounds with both cross-conjugated (m-phenylene) and linearly conjugated (2,5-thiophene) bridges have been prepared. As expected, the compounds undergo excitation to locally excited states followed by fluorescence from charge-transfer states. The m-phenylene-based systems exhibit slower charge-recombination rates presumably due to reduced electronic coupling through the cross-conjugated bridges. Interestingly, pairing the linearly conjugated 2,5-thiophene bridges also slows charge recombination. DFT calculations of frontier molecular orbitals show that the direct HOMO-LUMO transition is polarized orthogonal to the axis of charge transfer for these symmetrical macrocyclic architectures, reducing the electronic coupling. We believe the push-pull macrocycle design may be useful in engineering functional frontier molecular orbital symmetries.

  18. siRNA conjugates carrying sequentially assembled trivalent N-acetylgalactosamine linked through nucleosides elicit robust gene silencing in vivo in hepatocytes.

    Science.gov (United States)

    Matsuda, Shigeo; Keiser, Kristofer; Nair, Jayaprakash K; Charisse, Klaus; Manoharan, Rajar M; Kretschmer, Philip; Peng, Chang G; V Kel'in, Alexander; Kandasamy, Pachamuthu; Willoughby, Jennifer L S; Liebow, Abigail; Querbes, William; Yucius, Kristina; Nguyen, Tuyen; Milstein, Stuart; Maier, Martin A; Rajeev, Kallanthottathil G; Manoharan, Muthiah

    2015-05-15

    Asialoglycoprotein receptor (ASGPR) mediated delivery of triantennary N-acetylgalactosamine (GalNAc) conjugated short interfering RNAs (siRNAs) to hepatocytes is a promising paradigm for RNAi therapeutics. Robust and durable gene silencing upon subcutaneous administration at therapeutically acceptable dose levels resulted in the advancement of GalNAc-conjugated oligonucleotide-based drugs into preclinical and clinical developments. To systematically evaluate the effect of display and positioning of the GalNAc moiety within the siRNA duplex on ASGPR binding and RNAi activity, nucleotides carrying monovalent GalNAc were designed. Evaluation of clustered and dispersed incorporation of GalNAc units to the sense (S) strand indicated that sugar proximity is critical for ASGPR recognition, and location of the clustered ligand impacts the intrinsic potency of the siRNA. An array of nucleosidic GalNAc monomers resembling a trivalent ligand at or near the 3' end of the S strand retained in vitro and in vivo siRNA activity, similar to the parent conjugate design. This work demonstrates the utility of simple, nucleotide-based, cost-effective siRNA-GalNAc conjugation strategies.

  19. Folic acid-conjugated Fe{sub 3}O{sub 4} magnetic nanoparticles for hyperthermia and MRI in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Q.L.; Zheng, S.W. [College of Chemistry, Chemical Engineering and Materials Science and Key Laboratory of Organic Synthesis of Jiangsu Province, Soochow University, SIP, Suzhou 215123 (China); Hong, R.Y., E-mail: rhong@suda.edu.cn [College of Chemistry, Chemical Engineering and Materials Science and Key Laboratory of Organic Synthesis of Jiangsu Province, Soochow University, SIP, Suzhou 215123 (China); College of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou 350002 (China); Deng, S.M.; Guo, L. [The First Affiliated Hospital of Soochow University, Suzhou 215011 (China); Hu, R.L. [Department of Thoracic Surgery, Hangzhou First People' s Hospital, Hangzhou 310006 (China); Gao, B.; Huang, M.; Cheng, L.F. [College of Medicine, Soochow University, SIP, Suzhou 215123 (China); Liu, G.H. [Respiration Department, Suzhou Municipal Hospital (East-Section), Suzhou 215001 (China); Wang, Y.Q. [Key Laboratory of Environmental Materials and Engineering of Jiangsu Province, Yangzhou University, Yangzhou 225002 (China)

    2014-07-01

    The folic acid (FA)-conjugated Fe{sub 3}O{sub 4} magnetic nanoparticles (MNPs) were synthesized by co-precipitation of Fe{sup 3+} and Fe{sup 2+} solution followed by surface modification with carboxymethyl dextran (CMD) to form carboxymethyl group terminated MNPs, then FA was conjugated with the carboxyl group functionalized MNPs. The morphology and properties of obtained nanoparticles were characterized by X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), UV–visible spectra (UV–vis), transmission electron microscopy (TEM), dynamic light scattering (DLS), vibrating sample magnetometer (VSM) and thermogravimetric analysis (TGA). The FA-conjugated MNPs exhibited relatively high saturation magnetization and fast magneto-temperature response which could be applied to hyperthermia therapy. To determine the accurate targeting effect of FA, we chose FA-conjugated MNPs as MRI contrast enhancement agent for detection of KB cells with folate receptor over-expression in vitro and in vivo. The results show that these magnetic nanoparticles appear to be the promising materials for local hyperthermia and MRI.

  20. Phytosynthesis of gold nanoparticles using Mappia foetida leaves extract and their conjugation with folic acid for delivery of doxorubicin to cancer cells.

    Science.gov (United States)

    Yallappa, S; Manjanna, J; Dhananjaya, B L; Vishwanatha, U; Ravishankar, B; Gururaj, H

    2015-09-01

    Mappia foetida leaves extract is used as bioreductant for the synthesis of gold nanoparticles and their application in the efficient delivery of doxorubicin to human cancer cells is reported here. The formation of gold nanoparticles is evident from their characteristic optical absorption at ~560 nm. X-ray diffraction pattern of gold nanoparticles confirmed their fcc structure. Fourier transform infrared spectroscopy shows the bioactive molecules from plant extract capped on the surface of gold nanoparticles and conjugation of doxorubicin along with activated folic acid as navigational molecules for targeted drug delivery. Such a conjugation of gold nanoparticles is characterized by their weight loss, ~35-40 %, due to thermal degradation of plant biomass and conjugated drug along with receptor, as observed in thermogravimetric analysis. The spherical shaped gold nanoparticles (Φ 10-20 nm) are observed by field emission scanning electron microscopy and transmission electron microscopy images and the expected elemental composition by energy dispersive X-ray spectroscopy. Gold nanoparticles conjugated with activated folic acid and doxorubicin complex is found to be toxic for human cancer cells viz., MDA-MB-231, HeLa, SiHa and Hep-G2. Furthermore, the amount of drug released was maximum at pH 5.3 (an ambient condition for intravenous cancer drugs) followed by pH 7.2 and pH 6.8.

  1. In vitro detection of human breast cancer cells (SK-BR3) using herceptin-conjugated liquid crystal microdroplets as a sensing platform.

    Science.gov (United States)

    Ding, Wang; Gupta, Kailash Chandra; Park, Soo-Young; Kim, Young-Kyoo; Kang, Inn-Kyu

    2016-10-20

    The present study utilizes antibody-protein interactions to develop an LC microdroplet based biosensor for naked eye detection of SK-BR3 human breast cancer cells. The herceptin antibody-conjugated LC microdroplets were fabricated using 4-cyano-4'-pentyl biphenyl (5CB) as the liquid crystalline phase and sodium dodecyl sulfate (SDS) as the surfactant. The poly (styrene-b-acrylic acid) amphiphilic block copolymer (PS-b-PA) played a role as a modifier for the liquid crystalline interfaces. The 5CB molecules in the herceptin antibody-conjugated LC microdroplets have shown an orientation transition from radial to bipolar on selective interactions with targeted SK-BR3 breast cancer cells, which are over expressed by the human epidermal growth factor receptor 2-positive (HER2). The herceptin antibody-conjugated LC microdroplets are found to be highly selective in the detection of SK-BR3 cancer cells in the presence of control cells, such as KB cancer cells and fibroblast (FB), and also in the presence of 10% human blood plasma. The interaction forces of the SK-BR3 cancer cells were only effective in causing orientation transitions in 5CB molecules in the LC microdroplets, which clearly suggested that the herceptin antibody-conjugated LC microdroplets could be used as a selective biosensor for a real-time detection of SK-BR3 cancer cells in biological fluids.

  2. Microparticulate β-glucan vaccine conjugates phagocytized by dendritic cells activate both naïve CD4 and CD8 T cells in vitro.

    Science.gov (United States)

    Berner, Vanessa K; duPre, Sally A; Redelman, Doug; Hunter, Kenneth W

    2015-01-01

    Microparticulate β-glucan (MG) conjugated to vaccine antigen has been shown to serve as an effective adjuvant in vivo. To further study antigen presentation by MG:vaccine conjugates, bone marrow-derived dendritic cells (BMDC) were treated with MG conjugated to ovalbumin (OVA), then interacted with splenocytes from DO11.10 transgenic mice expressing an OVA peptide-specific T cell receptor. BMDC treated with MG:OVA induced significantly higher numbers of activated (CD25+CD69+) OVA-specific CD4+ T cells than BMDC treated with OVA alone. BMDC treated with MG:OVA upregulated CD86 and CD40 expression as well as MG alone, indicating that conjugation of OVA does not alter the immunostimulatory capacity of MG. Activation of CD8+ OVA-specific OT-1 cells showed that MG:OVA is also capable of enhancing cross-presentation by BMDC to CD8+ cytotoxic T cells. These results show that MG acts as an adjuvant to enhance antigen presentation by dendritic cells to naïve, antigen-specific CD4 and CD8 T cells.

  3. Self-Assembled Conjugated Polymer Nanometer Scale Devices

    Institute of Scientific and Technical Information of China (English)

    Wenping Hu; Hiroshi Nakashima; Keiichi Torimitsu; Yunqi Liu; Daoben Zhu

    2005-01-01

    @@ 1Introduction Nanometer scale devices, as the next generation devices of electronics, have got a worldwide attention and rapid development recently. Simultaneously, conjugated polymers have been applied in organic electronics successfully because of their outstanding electronic-photonic properties. However, as far as we know few reports have dealt with the fabrication of nanometer scale devices by using conjugated polymers, although the combination of nanometer scale devices and polymers will not only extend conjugated polymers to Nanoelectronics, but also excavate the behaviors of polymer molecules at nano-molecular level, such as the electron transport through polymer molecules. One reason for this case is due to the lack of rigidity for most polymers.It results in the failure to bridge them between electrodes or to stand on substrates, therefore, fails to be characterized by scanning probe microscopy. Another reason is that the non-functionalized end-group of most polymers is impossible to graft on substrates through chemical bonds. Here, we introduce a self-assembled conjugated polymer can be used to fabricate nanodevices by self-assembly. The conjugated polymer is a derivative of poly(p-phenyleneethynylene)s (PPE) with thioacetyl end groups (Fig. 1). In general, it is known that for self-assembling ideal nanojunctions the materials should possess: a) conductivity, b) rigidity (for wiring and bridging between electrodes), and c) connectivity (for covalent attachment to metallic or semiconductor solid surfaces). PPE provides good conductivity owing to its special π-conjugated configuration. It is also believed that in principle PPE molecules possess rigidity because of the presence of the triple bond in their molecules,which prevents the rotation of adjacent phenyl rings with respect to each other.

  4. Realization of a Dual Transmission Band Conjugate Omega Shaped Metamaterial

    Directory of Open Access Journals (Sweden)

    Asit Kumar Panda

    2011-11-01

    Full Text Available In this article we propose a new conjugate omega shaped structure for realization of left hand material. This new metamaterial (MTM is designed and simulated using CST MWS. The effective permittivity permeability are extracted from the transmission reflection data obtained by normal incident on the purposed structure. It is shown the purposed MTM exhibits DNG material property and negative refractive index in dual transmission band with wider band in frequency ranges from 3.35-6.37GHz and 12.53-16.7GHZ. The conjugate omegas structures are pseudo-chiral in nature, where both electric magnetic polarization are due to induced electric and magnetic fields.

  5. PREPARATION OF CHEMICALLY WELL-DEFINED CARBOHYDRATE DENDRIMER CONJUGATES

    DEFF Research Database (Denmark)

    2004-01-01

    A method for the synthesis of dendrimer conjugates having a well-defined chemical structure, comprising one or more carbohydrate moieties and one or more immunomodulating substances coupled to a dendrimer, is presented. First, the carbohydrate is bound to the dendrimer in a chemoselective manner....... Subsequently, the immunomodulating substance is also bound in a chemoselective manner, to give a dendrimer conjugate with a well-defined structure and connectivity and containing a precise, pre-determined ratio of carbohydrate to immunomodulating substance. The invention also relates to novel dendrimer...

  6. Product Summability Transform of Conjugate Series of Fourier Series

    Directory of Open Access Journals (Sweden)

    Vishnu Narayan Mishra

    2012-01-01

    Full Text Available A known theorem, Nigam (2010 dealing with the degree of approximation of conjugate of a signal belonging to Lipξ(t-class by (E,1(C,1 product summability means of conjugate series of Fourier series has been generalized for the weighted W(Lr,ξ(t, (r≥1,(t>0-class, where ξ(t is nonnegative and increasing function of t, by En1Cn1~ which is in more general form of Theorem 2 of Nigam and Sharma (2011.

  7. Morroniside cinnamic acid conjugate as an anti-inflammatory agent.

    Science.gov (United States)

    Takeda, Yoshinori; Tanigawa, Naomi; Sunghwa, Fortunatus; Ninomiya, Masayuki; Hagiwara, Makoto; Matsushita, Kenji; Koketsu, Mamoru

    2010-08-15

    A morroniside cinnamic acid conjugate was prepared and evaluated on E-selectin mediated cell-cell adhesion as an important role in inflammatory processes. 7-O-Cinnamoylmorroniside exhibited excellent anti-inflammatory activity (IC(50)=49.3 microM) by inhibiting the expression of E-selectin; further, it was more active than another cinnamic-acid-conjugated iridoid glycoside (harpagoside; IC(50)=88.2 microM), 7-O-methylmorroniside, and morroniside itself. As a result, 7-O-cinnamoylmorroniside was observed to be a potent inhibitor of TNF-alpha-induced E-selectin expression.

  8. A heterostructure composed of conjugated polymer and copper sulfide nanoparticles.

    Science.gov (United States)

    Narizzano, Riccardo; Erokhin, Victor; Nicolini, Claudio

    2005-08-25

    A heterostructure formed by a conjugated polymer and semiconducting nanoparticles was produced. The conjugated polymer was synthesized by oxidative copolymerization of 3-thiopheneacetic acid and 3-hexylthiophene, thus obtaining an amphiphilic polythiophene that allows the formation of a stable polymer layer at the air-water interface. Different numbers of monolayers were deposited on solid substrates. CuS nanoparticles were grown directly in the polymeric matrix using the carboxylic groups as nucleation centers. The reactions were monitored by quartz crystal microbalance, Brewster angle, and fluorescence microscopy. The heterostructure showed increased conductivity as compared to the pristine polymer.

  9. Clifford Algebras and Their Decomposition into Conjugate Fermionic Heisenberg Algebras

    Science.gov (United States)

    Catto, Sultan; Gürcan, Yasemin; Khalfan, Amish; Kurt, Levent; Kato La, V.

    2016-10-01

    We discuss a construction scheme for Clifford numbers of arbitrary dimension. The scheme is based upon performing direct products of the Pauli spin and identity matrices. Conjugate fermionic algebras can then be formed by considering linear combinations of the Clifford numbers and the Hermitian conjugates of such combinations. Fermionic algebras are important in investigating systems that follow Fermi-Dirac statistics. We will further comment on the applications of Clifford algebras to Fueter analyticity, twistors, color algebras, M-theory and Leech lattice as well as unification of ancient and modern geometries through them.

  10. Medicinal chemistry of drugs with active metabolites following conjugation.

    Science.gov (United States)

    Kalász, Huba; Petroianu, Georg; Hosztafi, Sándor; Darvas, Ferenc; Csermely, Tamás; Adeghate, Ernest; Siddiq, Afshan; Tekes, Kornélia

    2013-10-01

    Authorities of Drug Administration in the United States of America approved about 5000 drugs for use in the therapy or management of several diseases. About two hundred of these drugs have active metabolites and the knowledge of their medicinal chemistry is important both in medical practice and pharmaceutical research. This review gives a detailed description of the medicinal chemistry of drugs with active metabolites generated after conjugation. This review focused on glucuronide-, acetyl-, sulphate- and phosphate-conjugation of drugs, converting the drug into an active metabolite. This conversion essentially changed the lipophilicity of the drug.

  11. Synthesis and Characterization of π-Conjugated Dithiol

    Institute of Scientific and Technical Information of China (English)

    Hardy; S.O.Chan

    2007-01-01

    1 Results Organic compounds are able to act as active components for the preparation of electronics and optoelectronics.Fig.1 A new π-conjugated anthracene-based dithiol compoundA new π-conjugated anthracene-based dithiol compound has been synthesized and its optical properties were determined by UV-vis and PL spectroscopy.Its self-assembled monolayers on a gold surface have been prepared and characterized by spectroscopic ellipsometry and atomic force microscopy.The structures and properties of its SAM...

  12. Poly(trimethylsilylcyclooctatetraene): A soluble conjugated polyacetylene via olefin metathesis

    Energy Technology Data Exchange (ETDEWEB)

    Ginsburg, E.J.; Gorman, C.B.; Grubbs, R.H.; Marder, S.R. (California Institute of Technology, Pasadena (USA))

    1989-09-13

    highly conjugated polymers, such as polyacetylene, polythiophene, and poly(p-phenylene vinylene), have been the subject of intensive research due to their intriguing optical and electronic properties. These parent systems are highly desirable for experimental and theoretical studies due to their simplicity. Their intractability, however, has made characterization an arduous task, and insolubility has severely limited their applications. Researchers have successfully circumvented these obstacles by synthesizing soluble alkyl- and alkoxy-substituted polythiphenes and poly(p-phenylene vinylenes). Analogous soluble highly conjugated polyacetylene derivatives have proven more elusive. The authors report here the synthesis of such a polymer using ring-opening metathesis polymerization (ROMP).

  13. Emerging applications of conjugated polymers in molecular imaging.

    Science.gov (United States)

    Li, Junwei; Liu, Jie; Wei, Chen-Wei; Liu, Bin; O'Donnell, Matthew; Gao, Xiaohu

    2013-10-28

    In recent years, conjugated polymers have attracted considerable attention from the imaging community as a new class of contrast agent due to their intriguing structural, chemical, and optical properties. Their size and emission wavelength tunability, brightness, photostability, and low toxicity have been demonstrated in a wide range of in vitro sensing and cellular imaging applications, and have just begun to show impact in in vivo settings. In this Perspective, we summarize recent advances in engineering conjugated polymers as imaging contrast agents, their emerging applications in molecular imaging (referred to as in vivo uses in this paper), as well as our perspectives on future research.

  14. Peptide π-Electron Conjugates: Organic Electronics for Biology?

    Science.gov (United States)

    Ardoña, Herdeline Ann M; Tovar, John D

    2015-12-16

    Highly ordered arrays of π-conjugated molecules are often viewed as a prerequisite for effective charge-transporting materials. Studies involving these materials have traditionally focused on organic electronic devices, with more recent emphasis on biological systems. In order to facilitate the transition to biological environments, biomolecules that can promote hierarchical ordering and water solubility are often covalently appended to the π-electron unit. This review highlights recent work on π-conjugated systems bound to peptide moieties that exhibit self-assembly and aims to provide an overview on the development and emerging applications of peptide-based supramolecular π-electron systems.

  15. Synthesis and photocurrent response of porphyrin-containing conjugated polymers

    Institute of Scientific and Technical Information of China (English)

    ZHAO Jinling; LI Binsong; BO Zhishan

    2006-01-01

    Porphyrin-containing conjugated polymers with fluorene or carbazole as spacer groups were prepared by Sonogashira cross-coupling reactions. The polymers were of high molecular weight and the flexible alkyl chains on fluorene or carbazole units made the conjugated polymers soluble in common organic solvents, such as THF and methylene chloride. The polymers could form high quality durable films from solution casting. Their optical and photocurrent responsive properties were investigated. It was found that the photocurrent response was directly proportional to the content of porphyrin. The incorporation of carbazole units into the polymer chains also gave positive contribution to the photocurrent generation in some extent.

  16. Integrable Lattice Models for Conjugate $A^{(1)}_n$

    CERN Document Server

    Behrend, R E; Behrend, Roger E.; Evans, David E.

    2004-01-01

    A new class of $A^{(1)}_n$ integrable lattice models is presented. These are interaction-round-a-face models based on fundamental nimrep graphs associated with the $A^{(1)}_n$ conjugate modular invariants, there being a model for each value of the rank and level. The Boltzmann weights are parameterized by elliptic theta functions and satisfy the Yang-Baxter equation for any fixed value of the elliptic nome q. At q=0, the models provide representations of the Hecke algebra and are expected to lead in the continuum limit to coset conformal field theories with torus partition functions described by the $A^{(1)}_n$ conjugate modular invariants.

  17. Convexity of Spheres in a Manifold without Conjugate Points

    Indian Academy of Sciences (India)

    Akhil Ranjan; Hemangi Shah

    2002-11-01

    For a non-compact, complete and simply connected manifold without conjugate points, we prove that if the determinant of the second fundamental form of the geodesic spheres in is a radial function, then the geodesic spheres are convex. We also show that if is two or three dimensional and without conjugate points, then, at every point there exists a ray with no focal points on it relative to the initial point of the ray. The proofs use a result from the theory of vector bundles combined with the index lemma.

  18. Conjugate heat and mass transfer in heat mass exchanger ducts

    CERN Document Server

    Zhang, Li-Zhi

    2013-01-01

    Conjugate Heat and Mass Transfer in Heat Mass Exchanger Ducts bridges the gap between fundamentals and recent discoveries, making it a valuable tool for anyone looking to expand their knowledge of heat exchangers. The first book on the market to cover conjugate heat and mass transfer in heat exchangers, author Li-Zhi Zhang goes beyond the basics to cover recent advancements in equipment for energy use and environmental control (such as heat and moisture recovery ventilators, hollow fiber membrane modules for humidification/dehumidification, membrane modules for air purification, desi

  19. Side Chain Engineering in Solution-Processable Conjugated Polymers

    KAUST Repository

    Mei, Jianguo

    2014-01-14

    Side chains in conjugated polymers have been primarily utilized as solubilizing groups. However, these side chains have roles that are far beyond. We advocate using side chain engineering to tune a polymer\\'s physical properties, including absorption, emission, energy level, molecular packing, and charge transport. To date, numerous flexible substituents suitable for constructing side chains have been reported. In this Perspective article, we advocate that the side chain engineering approach can advance better designs for next-generation conjugated polymers. © 2013 American Chemical Society.

  20. Electronic states of emodin and its conjugate base

    DEFF Research Database (Denmark)

    Nguyen, Son Chi; Hansen, Bjarke Knud Vilster; Hoffmann, Søren Vrønning;

    2008-01-01

    The electronic transitions of emodin (1,3,8-trihydroxy-6-methyl-9,10-anthraquinone, E) and its conjugate base (3-oxido-6-methyl-1,8-dihydroxy-9,10-anthraquinone, Ecb) were investigated by UV-Vis linear dichroism (LD) spectroscopy on molecular samples aligned in stretched poly(vinylalcohol). The e......The electronic transitions of emodin (1,3,8-trihydroxy-6-methyl-9,10-anthraquinone, E) and its conjugate base (3-oxido-6-methyl-1,8-dihydroxy-9,10-anthraquinone, Ecb) were investigated by UV-Vis linear dichroism (LD) spectroscopy on molecular samples aligned in stretched poly...

  1. Anti-neuropilin 1 antibody Fab' fragment conjugated liposomal docetaxel for active targeting of tumours.

    Science.gov (United States)

    Manjappa, Arehalli S; Goel, Peeyush N; Gude, Rajiv P; Ramachandra Murthy, Rayasa S

    2014-09-01

    Neuropilin-1, a transmembrane receptor entailed in wide range of human tumour cell lines and diverse neoplasms, mediates the effects of VEGF and Semaphorins during the processes of cellular proliferation, survival and migration. In view of this, we had developed and evaluated in vitro and in vivo efficacy of anti-neuropilin-1 immunoliposomes against neuropilin-1 receptor expressing tumours. The PEGylated liposomes loaded with docetaxel were prepared using thin film hydration method. Functionalised PEGylated liposomes were prepared using post-insertion technique. Anti-neuropilin-1 immunoliposomes were prepared by covalently conjugating Fab' fragments of neuropilin-1 antibody to functionalised PEGylated liposomes via thioether linkage. In vivo evaluation of Taxotere and liposomal formulations was performed using intradermal tumour model to demonstrate anti-angiogenic and tumour regression ability. The modified Fab' fragments and immunoliposomes were found to be immunoreactive against A549 cells. Further, docetaxel loaded PEGylated liposomes and PEGylated immunoliposomes demonstrated higher in vitro cytotoxicity than Taxotere formulation at the same drug concentration and exposure time. The live imaging showed distinctive cellular uptake of functional immunoliposomes. Further, significant decrease in micro-blood vessel density and tumour volumes was observed using bio-engineered liposomes. The results clearly highlight the need to seek neuropilin-1 as one of the prime targets in developing an anti-angiogenic therapy.

  2. Dietary conjugated linoleic acid modify gene expression in liver, muscles, and fat tissues of finishing pigs.

    Science.gov (United States)

    Tous, N; Theil, P K; Lauridsen, C; Lizardo, R; Vilà, B; Esteve-Garcia, E

    2012-12-01

    The aim of this study was to investigate underlying mechanisms of dietary conjugated linoleic acid (CLA) on lipid metabolism in various tissues of pigs. Sixteen gilts (73 ± 3 kg) were fed a control (containing sunflower oil) or an experimental diet in which 4% of sunflower oil was replaced by CLA, and slaughtered at an average BW of 117 ± 4.9 kg. Transcription of peroxisome proliferator-activated receptor alpha (PPARα), peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FAS), sterol regulatory element binding protein (SREBP1), acetyl-CoA carboxylase (ACC), lipoprotein lipase (LPL), delta-6-desaturase (D6D), and stearoyl CoA desaturase (SCD) were determined by real-time PCR in longissimus thoracis (LT) and semimembranosus (SM) muscles, LT subcutaneous and SM intermuscular fat, and in the liver. Fatty acid (FA) composition was analyzed using gas chromatography in these tissues, except for SM intermuscular fat. Dietary CLA increased PPARγ in LT muscle (P tissues studied (P muscle and liver (SREBP1, both P muscle and reduced (P muscle and intermuscular fat. Saturated FA were increased in all studied tissues (P tissue-specific way by CLA. It was concluded that dietary CLA affected transcription of genes and fat metabolism in a tissue-specific manner.

  3. Ultrasound Molecular Imaging of Angiogenesis Using Vascular Endothelial Growth Factor-Conjugated Microbubbles

    Science.gov (United States)

    Wang, Jianjun; Qin, Bin; Chen, Xucai; Wagner, William R.; Villanueva, Flordeliza S.

    2017-01-01

    Imaging of angiogenesis receptors could provide a sensitive and clinically useful method for detecting neovascularization such as occurs in malignant tumors, and responses to anti-angiogenic therapies for such tumors. We tested the hypothesis that microbubbles (MB) tagged with human VEGF121 (MBVEGF) bind to the kinase insert domain receptor (KDR) in vitro and angiogenic endothelium in vivo, and that this specific binding can be imaged on a clinical ultrasound system. In this work, targeted adhesion of MBVEGF was evaluated in vitro using a parallel plate flow system containing adsorbed recombinant human KDR. There was more adhesion of MBVEGF to KDR-coated plates when the amount of VEGF121 on each MB or KDR density on the plate was increased. MBVEGF adhesion to KDR-coated plates decreased with increasing wall shear rate. On intravital microscopic imaging of bFGF-stimulated rat cremaster muscle, there was greater microvascular adhesion of MBVEGF compared to that of isotype IgG-conjugated control MB (MBCTL). To determine if MBVEGF could be used to ultrasonically image angiogenesis, ultrasound imaging was performed in mice bearing squamous cell carcinoma after intravenous injection of MBVEGF. Ultrasound videointensity enhancement in tumor was significantly higher for MBVEGF (17.3±9.7 dB) compared to MBCTL (3.8±4.4 dB, n=6, ptumor angiogenesis and could be extended to other applications such as molecular monitoring of therapeutic angiogenesis or anti-angiogenic therapies in cardiovascular disease or cancer. PMID:28165246

  4. Potential of antibody–drug conjugates and novel therapeutics in breast cancer management

    Directory of Open Access Journals (Sweden)

    Lianos GD

    2014-03-01

    Full Text Available Georgios D Lianos,1 Konstantinos Vlachos,2 Odysseas Zoras,3 Christos Katsios,1 William C Cho,4 Dimitrios H Roukos11Centre for Biosystems and Genomic Network Medicine, Ioannina University, Ioannina, Greece; 2Department of Surgery, Ioannina University Hospital, Ioannina, Greece; 3Department of Surgical Oncology, Heraklion University Hospital, Crete, Greece; 4Department of Clinical Oncology, Queen Elizabeth Hospital, Hong KongAbstract: Progress in the treatment of cancer over the past decade has been slow. Targeting a mutated gene of an individual patient tumor, tumor-guided agents, and the first draft of the human genome sequence have created an overenthusiasm to achieve personalized medicine. However, we now know that this effort is misleading. Extreme interpatient and intratumor heterogeneity, scarce knowledge in how genome-wide mutational landscape and epigenetic changes affect transcriptional processes, gene expression, signaling transduction networks and cell regulation, and clinical assessment of temporary efficacy of targeted drugs explain the limitations of these currently available agents. Trastuzumab and a few other monoclonal antibodies or small-molecule tyrosine kinase inhibitors (TKIs represent an exception to this rule. By blocking ligand-binding receptor in patients with human epidermal growth factor receptor 2 (HER2 amplification and overexpression, trastuzumab added to chemotherapy in HER2-positive patients has been proven to provide significant overall survival benefit in both metastatic and adjuvant settings. Lapatinib, a small-molecule dual inhibitor (TKI of both HER2 and EGFR (epidermal growth factor receptor pathways, has an antitumor activity translated into progression-free survival benefit in HER2-positive metastatic patients previously treated with a taxane, an anthracycline, and trastuzumab. Despite these advances, ~25% of patients with HER2-positive breast cancer experience recurrence in the adjuvant setting, while in

  5. Light-emitting conjugated polymers with microporous network architecture: interweaving scaffold promotes electronic conjugation, facilitates exciton migration, and improves luminescence.

    Science.gov (United States)

    Xu, Yanhong; Chen, Long; Guo, Zhaoqi; Nagai, Atsushi; Jiang, Donglin

    2011-11-09

    Herein we report a strategy for the design of highly luminescent conjugated polymers by restricting rotation of the polymer building blocks through a microporous network architecture. We demonstrate this concept using tetraphenylethene (TPE) as a building block to construct a light-emitting conjugated microporous polymer. The interlocked network successfully restricted the rotation of the phenyl units, which are the major cause of fluorescence deactivation in TPE, thus providing intrinsic luminescence activity for the polymers. We show positive "CMP effects" that the network promotes π-conjugation, facilitates exciton migration, and improves luminescence activity. Although the monomer and linear polymer analogue in solvents are nonemissive, the network polymers are highly luminescent in various solvents and the solid state. Because emission losses due to rotation are ubiquitous among small chromophores, this strategy can be generalized for the de novo design of light-emitting materials by integrating the chromophores into an interlocked network architecture.

  6. Bioactivation of cysteine conjugates of 1-nitropyrene oxides by cysteine conjugate beta-lyase purified from Peptostreptococcus magnus.

    OpenAIRE

    Kataoka, K; Kinouchi, T; Akimoto, S; Ohnishi, Y

    1995-01-01

    To determine the role of cysteine conjugate beta-lyase (beta-lyase) in the metabolism of mutagenic nitropolycyclic aromatic hydrocarbons, we determined the effect of beta-lyase on the mutagenicities and DNA binding of cysteine conjugates of 4,5-epoxy-4,5-dihydro-1-nitropyrene (1-NP 4,5-oxide) and 9,10-epoxy-9,10-dihydro-1-nitropyrene (1-NP 9,10-oxide), which are detoxified metabolites of the mutagenic compound 1-nitropyrene. We purified beta-lyase from Peptostreptococcus magnus GAI0663, since...

  7. Conjugative Transfer and cis-Mobilization of a Genomic Island by an Integrative and Conjugative Element of Streptococcus agalactiae

    OpenAIRE

    Puymège, Aurore; Bertin, Stéphane; Chuzeville, Sarah; Guédon, Gérard; Payot, Sophie

    2013-01-01

    Putative integrative and conjugative elements (ICEs), i.e., genomic islands which could excise, self-transfer by conjugation, and integrate into the chromosome of the bacterial host strain, were previously identified by in silico analysis in the sequenced genomes of Streptococcus agalactiae (M. Brochet et al., J. Bacteriol. 190:6913–6917, 2008). We investigated here the mobility of the elements integrated into the 3′ end of a tRNALys gene. Three of the four putative ICEs tested were found to ...

  8. Synthesis of Bis (silyloxy) Cross-Conjugated Polyenes and Their Sequential Ring Formations via Electrocyclization

    OpenAIRE

    Wada, Eiji; Kanemasa, Shuji; Kimura, Nobuo; KIMURA, Hirohiko; Tsuge, Otohiko

    1989-01-01

    Presented are the synthesis of several bis(silyloxy) cross-conjugated polyenes and some synthetic utilization of these new types of conjugation systems via thermal or photochemical electrocyclization.

  9. Realization of Large Area Flexible Fullerene - Conjugated Polymer Photocells : A Route to Plastic Solar Cells

    NARCIS (Netherlands)

    Brabec, C.J.; Padinger, F.; Hummelen, J.C.; Janssen, R.A.J.; Sariciftci, N.S.

    1999-01-01

    Bulk donor - acceptor heterojunctions between conjugated polymers and fullerenes have been utilized for photovoltaic devices with quantum efficiencies of around 1%. These devices are based on the photoinduced, ultrafast electron transfer between non degenerate ground state conjugated polymers and fu

  10. Binding of antibodies to acetylcholine receptors in Electrophorus and Torpedo electroplax membranes

    Science.gov (United States)

    1978-01-01

    Antisera against purified acetylcholine receptors from the electric tissues of Torpedo californica and of Electrophorus electricus were raised in rabbits. The antisera contain antibodies which bind to both autologous and heterologous receptors in solution as shown by an immunoprecipitation assay. Antibodies in both types of antisera bind specifically to the postjunctional membrane on the innervated surface of the intact electroplax from Electrophorus electric tissue as demonstrated by an indirect immunohistochemical procedure using horseradish peroxidase conjugated to anti-rabbit IgG. Only anti- Electrophorus receptor antisera, however, cause inhibition of the receptor-mediated depolarization of the intact Electrophorus electroplax. The lack of inhibition by anti-Torpedo receptor antibodies, which do bind, suggests that the receptor does not undergo extensive movement during activity. The binding of anti-Torpedo antibodies to receptor-rich vesicles prepared by subcellular fractionation of Torpedo electric tissue was demonstrated by both direct and indirect immunohistochemical methods using ferritin conjugates. These vesicles can be conveniently collected and prepared for electron microscopy on Millipore filters, a procedure requiring only 25 micrograms of membrane protein per filter. In addition, it was possible to visualize the binding of anti-Torpedo receptor antibodies directly, without ferritin. These anti-Torpedo receptor antibodies, however, do not inhibit the binding of acetylcholine or of alpha- neurotoxin to receptor in Torpedo microsacs but do inhibit binding of alpha-neurotoxin to Torpedo receptor in Triton X-100 solution. It is likely that the principal antigenic determinants on receptor are at sites other than the acetylcholine-binding sites and that inhibition of receptor function, when it occurs, may be due to a stabilization by antibody binding of an inactive conformational state. PMID:344325

  11. Accessing Structurally Diverse Near-Infrared Cyanine Dyes for Folate Receptor-Targeted Cancer Cell Staining.

    Science.gov (United States)

    König, Sandra G; Krämer, Roland

    2017-03-24

    Folate receptor (FR) targeting is one of the most promising strategies for the development of small-molecule based cancer imaging agents since the FR is highly overexpressed on the surface of many cancer cell types. FR-targeted conjugates of NIR emissive cyanine dyes are in advanced clinical trials for fluorescence-guided surgery and are valuable research tools for optical molecular imaging in animal models. Only a small number of promising conjugates has been evaluated so far. Analysis of structure-performance relations to identify critical factors modulating the performance of targeted conjugates is essential for successful further optimization. This contribution addresses the need for convenient synthetic access to structurally diverse NIR-emissive cyanine dyes for conjugation with folic acid. Structural variations were introduced to readily available cyanine precursors in particular via C-C-coupling reactions including Suzuki- and (for the first time with these types of dyes) Sonogashira cross couplings. Photophysical properties such as absorbance maxima, brightness, and photostability are highly dependent on the molecular structure. Selected modified cyanines were conjugated to folic acid for cancer cell targeting. Several conjugates display a favorable combination of high fluorescence brightness and photostability with high affinity to FR positive cancer cells, and enable the selective imaging of these cells with low background.

  12. Sub-nanometer control of the interlayer spacing in thin films of intercalated rodlike conjugated molecules.

    Science.gov (United States)

    Vogel, Jörn-Oliver; Salzmann, Ingo; Opitz, Ricarda; Duhm, Steffen; Nickel, Bert; Rabe, Jürgen P; Koch, Norbert

    2007-12-27

    Organic molecular beam co-deposition of rodlike conjugated molecules with an alkylated analogue resulted in thin film structures with layers of alternating semiconducting (conjugated molecular parts) and insulating (alkyl parts) character. By varying the alkylated molecule ratio, we could adjust the distance between conjugated layers with sub-nanometer precision, exploiting the mechanical flexibility of the alkyl chains. Furthermore, due to mutual molecular intercalation, mixed layers containing two conjugated moieties with vastly different electronic properties could be fabricated.

  13. Synthesis and Antiproliferative Activity of Silybin Conjugates with Salinomycin and Monensin.

    Science.gov (United States)

    Antoszczak, Michał; Klejborowska, Greta; Kruszyk, Monika; Maj, Ewa; Wietrzyk, Joanna; Huczyński, Adam

    2015-12-01

    Aiming at development of multitarget drugs for the anticancer treatment, new silybin (SIL) conjugates with salinomycin (SAL) and monensin (MON) were synthesized, in mild esterification conditions, and their antiproliferative activity was studied. The conjugates obtained exhibit anticancer activity against HepG2, LoVo and LoVo/DX cancer cell lines. Moreover, MON-SIL conjugate exhibits higher anticancer potential and better selectivity than the corresponding SAL-SIL conjugate.

  14. Unconjugated Bile Salts Shuttle Through Hepatocyte Peroxisomes for Taurine Conjugation

    NARCIS (Netherlands)

    Rembacz, Krzysztof P.; Woudenberg, Jannes; Hoekstra, Mark; Jonkers, Elles Z.; van den Heuvel, Fiona A. J.; Buist-Homan, Manon; Woudenberg-Vrenken, Titia E.; Rohacova, Jana; Luisa Marin, M.; Miranda, Miguel A.; Moshage, Han; Stellaard, Frans; Faber, Klaas Nico

    2010-01-01

    Bile acid-CoA.amino acid N-acyltransferase (BAAT) conjugates bile salts to glycine or taurine, which is the final step in bile salt biosynthesis In addition, BAAT is required for reconjugation of bile salts in the enterohepatic circulation Recently, we showed that BAAT is a peroxisomal protein,

  15. Programmable multimetallic linear nanoassemblies of ruthenium-DNA conjugates

    OpenAIRE

    Irvoas, Joris; Noirot, Arielle; Chouini-Lalanne, Nadia; Reynes, Olivier; Garrigues, Jean-Christophe; Sartor, Valérie

    2012-01-01

    International audience; A new ruthenium-DNA conjugates family was synthesized, made up of a ruthenium complex bound to one or two identical DNA strands of 14-58 nucleotides. The formation of controlled linear nanoassemblies containing one to seven ruthenium complexes is described.

  16. Excitons in conjugated polymers: Do we need a paradigma change?

    Energy Technology Data Exchange (ETDEWEB)

    Beenken, Wichard J.D. [Department of Theoretical Physics I, Ilmenau University of Thechnology (Germany)

    2009-12-15

    We have previously shown that both, polymer conformation and dynamics are crucial for the exciton transport in conjugated polymers. Thereby we found that the usual Foerster-type hopping transfer model - even if one applies the line-dipole approximation - falls short in one crucial aspect: the nature of the sites the excitons are transferred between is still unclear. We found that the simple model of spectroscopic units defined as segments of the polymer chains separated by structural defects breaking the {pi}-conjugation is only justified for chemical defects like hydrogenated double bonds, or extreme gauche (90 ) torsions between the monomers. Both defects are far too rare in a well-prepared conjugated polymer to explain the mean spectroscopic-unit length of typically 6-7 monomers. Meanwhile, also the concept of dynamical formation of the spectroscopic units, we had previously suggested, has also failed. Thus the question of a paradigma change concerning the exciton transport in conjugated polymers appears on the agenda. (Abstract Copyright [2009], Wiley Periodicals, Inc.)

  17. Novel Bipolar Conjugated Polymer Containing Both Triphenylamine and Oxadizole Units

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A novel bipolar conjugated polymer containing triphenylamine and 1, 3, 4-oxadiazole units was synthesized by Suzuki reaction. Its structure and properties were characterized by NMR, IR, UV-Vis, PL spectroscopy and electrochemical measurement. The photoluminescent spectroscopy and cyclic voltammograms measurement demonstrated that the resulting polymer shows blue emission (477 nm) and possesses both electron and hole-transporting property.

  18. Photorefractive dynamic holography using self-pumped phase conjugate beam

    Indian Academy of Sciences (India)

    Arun Anand; C S Narayanamurthy

    2006-03-01

    Dynamic holography in photorefractive materials using self-pumped phase conjugate beam of the object beam itself as the other writing beam is proposed. Our detailed theoretical analysis shows four-fold increase in the diffraction efficiency of dynamic holograms if recorded using this geometry even in photorefractive crystal like BTO (having low optical activity) without applying external field. Detailed theoretical analysis is given.

  19. Genomic comparison of archaeal conjugative plasmids from Sulfolobus

    DEFF Research Database (Denmark)

    Greve, Bo Bjørn

    2004-01-01

    All of the known self-transmissable plasmids of the Archaea have been found in the genus Sulfolobus. To gain more insight into archaeal conjugative processes, four newly isolated self-transmissable plasmids, pKEF9, pHVE14, pARN3 and pARN4, were sequenced and subjected to a comparative sequence...

  20. Abnormal glutathione conjugation in patients with tyrosinaemia type I

    NARCIS (Netherlands)

    Bergman, DJW; PollThe, BT; Smit, GPA; Breimer, DD; Duran, M; Smeitink, JAM

    1997-01-01

    Previous studies have suggested that tyrosinaemia type I may be associated with reduced glutathione availability due to conjugation of tyrosinaemia-associated reactive intermediates with glutathione. In the present study, the glutathione/glutathione S-transferase system of two tyrosinaemia patients