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Nonspecific Interactions (nonspecific + interaction)
Selected AbstractsA Molecular Brush Approach to Enhance Quantum Yield and Suppress Nonspecific Interactions of Conjugated Polyelectrolyte for Targeted Far-Red/Near-Infrared Fluorescence Cell ImagingADVANCED FUNCTIONAL MATERIALS, Issue 17 2010Kan-Yi Pu Abstract A red-fluorescent conjugated polyelectrolyte (CPE, P2) is grafted with dense poly(ethylene glycol) (PEG) chains via click chemistry and subsequently modified with folic acid to form a molecular brush based cellular probe (P4). P4 self-assembles into a core,shell nanostructure in aqueous medium with an average size of 130 nm measured by laser light scattering. As compared to P2, P4 possesses not only a substantially higher quantum yield (11%), but also reduced nonspecific interactions with biomolecules in aqueous medium due to the shielding effect of PEG. In conjunction with its high photostability and low cytotoxicity, utilization of P4 as a far-red/near-infrared cellular probe allows for effective visualization and discrimination of MCF-7 cancer cells from NIH-3T3 normal cells in a high contrast, selective, and nonviral manner. This study thus demonstrates a flexible molecular brush approach to overcome the intrinsic drawbacks of CPEs for advanced bioimaging applications. [source] A Molecular Brush Approach to Enhance Quantum Yield and Suppress Nonspecific Interactions of Conjugated Polyelectrolyte for Targeted Far-Red/Near-Infrared Fluorescence Cell ImagingADVANCED FUNCTIONAL MATERIALS, Issue 17 2010Kan-Yi Pu Abstract A red-fluorescent conjugated polyelectrolyte (CPE, P2) is grafted with dense poly(ethylene glycol) (PEG) chains via click chemistry and subsequently modified with folic acid to form a molecular brush based cellular probe (P4). P4 self-assembles into a core,shell nanostructure in aqueous medium with an average size of 130 nm measured by laser light scattering. As compared to P2, P4 possesses not only a substantially higher quantum yield (11%), but also reduced nonspecific interactions with biomolecules in aqueous medium due to the shielding effect of PEG. In conjunction with its high photostability and low cytotoxicity, utilization of P4 as a far-red/near-infrared cellular probe allows for effective visualization and discrimination of MCF-7 cancer cells from NIH-3T3 normal cells in a high contrast, selective, and nonviral manner. This study thus demonstrates a flexible molecular brush approach to overcome the intrinsic drawbacks of CPEs for advanced bioimaging applications. [source] Uniformly Nucleobase-Functionalized ,-Peptide Helices: Watson,Crick Pairing or Nonspecific AggregationEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 33 2007Angelina Weiß Abstract The organization and architecture of helices is fundamental in folding of protein tertiary structures. Therefore, stable ,-peptide helices are used as models for the selective organization of secondary structures. Nucleobases are already established as recognition elements to organize two ,-peptide helices in antiparallel orientation. The investigation of ,-peptide helices uniformly functionalized with one type of nucleobases provided further insight in the recognition mode and requirements for specific interaction within the linear and very rigid helical backbone topology. Specific helix interaction based on base pair recognition is predominant as soon as Watson,Crick pairing is allowed. If the hydrogen bonding donor/acceptor pattern prohibits the Watson,Crick geometry, a quite stable nonspecific interaction was found based on aromatic interactions or on a nonspecific hydrogen bonding network. The latter aggregation was also confirmed with tyrosine side chains.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] Enhanced Growth Inhibition of Hepatic Multicellular Tumor Spheroids by Lactosylated Poly(ethylene glycol)-siRNA Conjugate Formulated in PEGylated PolyplexesCHEMMEDCHEM, Issue 9 2007Motoi Oishi Prof. Abstract PEGylated polyplexes (lac-PEGylated polyplexes) composed of poly(L -lysine) and lactosylated poly(ethylene glycol)-small interfering RNA conjugate, which inhibits the RecQL1 gene product, were revealed to show an appreciable growth inhibition of multicellular HuH-7 spheroids (human hepatocarcinoma cell lines) for up to 21 days (IC50=6,nM); this system used as an in,vitro three-dimensional (3D) model mimicking the in,vivo biology of tumors. The PEGylated polyplexes thus prepared had a size of approximately 110,nm with clustered lactose moieties on their periphery as targeting ligands for the asialoglycoprotein-receptor-expressing HuH-7 cells. In contrast, OligofectAMINE/siRNA (cationic lipoplex) was observed to have almost no growth-inhibitory effect against HuH-7 spheroids, even though the lipoplex showed a stronger growth-inhibitory effect than the lac-PEGylated polyplexes on conventional monolayer-cultured HuH-7 cells. The FITC-tagged conjugate in the lac-PEGylated polyplexes showed smooth penetration into the HuH-7 spheroids compared with that in the lipoplexes, as observed by confocal fluorescence-scanning microscopy. This indicates that the small size of approximately 100,nm and the reduced nonspecific interaction due to the nonionic and hydrophilic lactosylated PEG layer contributes to the smooth penetration of the PEGylated polyplexes into the spheroid interior, eventually facilitating their uptake into the cells composing the spheroids. Cellular apoptosis indicating programmed cell death was also observed in the HuH-7 spheroids treated with the PEGylated polyplexes, revealing that the observed growth inhibition was indeed induced by the RNAi of the RecQL1 siRNA. These data suggest that the smart PEGylated polyplexes can indeed penetrate into the multiple cell layers of 3D tumor masses in,vivo, exerting therapeutic effects through the RNAi. [source] Validation of a modified Flory-Huggins concept for description of hydrophobic organic compound sorption on dissolved humic substancesENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 9 2002Anett Georgi Abstract Sorption coefficients(KDOC) on dissolved organic matter (DOM) have been determined by means of solid-phase microextraction (SPME) for hydrophobic organic compounds (HOCs) of various classes, for example, polycyclic aromatic hydrocarbons (PAHs), noncondensed arenes, and alkanes. Relating the KDOC values obtained to the octanol-water partition coefficients of the solutes results in class-specific correlations. Obviously, PAHs have a higher affinity to DOM than other HOCs with equal KOW values. The different KDOC to KOW correlations can be combined into one general formula based on a modified Flory-Huggins concept. It permits the calculation of sorption coefficients from the solubility parameters (,) and KOW values of the solutes and the solubility parameter of the sorbent. The latter value, which is specific to the DOM under consideration, can be determined from a single measured sorption coefficient. By applying the proposed Flory-Huggins concept, which is based on the presumption of nonspecific interactions between HOCs and DOM, the different affinities of PAHs, noncondensed arenes, and alkanes to DOM can be accurately predicted. [source] A Molecular Brush Approach to Enhance Quantum Yield and Suppress Nonspecific Interactions of Conjugated Polyelectrolyte for Targeted Far-Red/Near-Infrared Fluorescence Cell ImagingADVANCED FUNCTIONAL MATERIALS, Issue 17 2010Kan-Yi Pu Abstract A red-fluorescent conjugated polyelectrolyte (CPE, P2) is grafted with dense poly(ethylene glycol) (PEG) chains via click chemistry and subsequently modified with folic acid to form a molecular brush based cellular probe (P4). P4 self-assembles into a core,shell nanostructure in aqueous medium with an average size of 130 nm measured by laser light scattering. As compared to P2, P4 possesses not only a substantially higher quantum yield (11%), but also reduced nonspecific interactions with biomolecules in aqueous medium due to the shielding effect of PEG. In conjunction with its high photostability and low cytotoxicity, utilization of P4 as a far-red/near-infrared cellular probe allows for effective visualization and discrimination of MCF-7 cancer cells from NIH-3T3 normal cells in a high contrast, selective, and nonviral manner. This study thus demonstrates a flexible molecular brush approach to overcome the intrinsic drawbacks of CPEs for advanced bioimaging applications. [source] A Molecular Brush Approach to Enhance Quantum Yield and Suppress Nonspecific Interactions of Conjugated Polyelectrolyte for Targeted Far-Red/Near-Infrared Fluorescence Cell ImagingADVANCED FUNCTIONAL MATERIALS, Issue 17 2010Kan-Yi Pu Abstract A red-fluorescent conjugated polyelectrolyte (CPE, P2) is grafted with dense poly(ethylene glycol) (PEG) chains via click chemistry and subsequently modified with folic acid to form a molecular brush based cellular probe (P4). P4 self-assembles into a core,shell nanostructure in aqueous medium with an average size of 130 nm measured by laser light scattering. As compared to P2, P4 possesses not only a substantially higher quantum yield (11%), but also reduced nonspecific interactions with biomolecules in aqueous medium due to the shielding effect of PEG. In conjunction with its high photostability and low cytotoxicity, utilization of P4 as a far-red/near-infrared cellular probe allows for effective visualization and discrimination of MCF-7 cancer cells from NIH-3T3 normal cells in a high contrast, selective, and nonviral manner. This study thus demonstrates a flexible molecular brush approach to overcome the intrinsic drawbacks of CPEs for advanced bioimaging applications. [source] Achieving efficient delivery of morpholino oligos in cultured cellsGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 3 2001Paul A. Morcos Abstract Summary: One of the many features that make morpholino oligos unique among the antisense structural types is an uncharged backbone. While this feature eliminates the nonspecific interactions of traditional S-oligos, it also renders the morpholino undeliverable via the traditional lipid-based delivery systems. This article describes a highly efficient method of delivering morpholino oligos into adherent and nonadherent cultured cells. In this system, a nonionic morpholino oligo is paired to a complementary DNA "carrier." The DNA is then bound electrostatically to a partially ionized, weakly-basic ethoxylated polyethylenimine (EPEI). This morpholino/DNA/EPEI complex is efficiently endocytosed, and when the pH drops within the endosome, the EPEI more fully ionizes, resulting in permeabilization of the endosomal membrane and release of the morpholino into the cytosol. This article describes optimization of delivery in HeLa cells and provides the basis for delivery in any cultured endocytic cell type. genesis 30:94,102, 2001. © 2001 Wiley-Liss, Inc. [source] Electrosynthesized Surface-Imprinted Conducting Polymer Microrods for Selective Protein RecognitionADVANCED MATERIALS, Issue 22 2009Anna Menaker Novel surface-imprinted conducting polymer microrods are shown to selectively recognize the template protein, as demonstrated by competitive binding assays using fluorescence detection. The electrochemical template synthesis provides means for controlled fabrication and spatial confinement of the PEDOT/PSS polymer proposed in this work, which exhibits extraordinary low nonspecific interactions and is effectively turned into a selective protein sorbent upon imprinting. [source] Synthesis, pharmacology, crystal properties, and quantitative solvation studies from a drug transport perspective for three new 1,2,4-thiadiazolesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2010German L. Perlovich Abstract A novel 1,2,4-thiadiazoles were synthesized. Crystal structures of these compounds were solved by X-ray diffraction experiments and comparative analysis of molecular conformational states, packing architecture, and hydrogen bonds networks were carried out. Thermodynamic aspects of sublimation processes of studied compounds were determined using temperature dependencies of vapor pressure. Thermophysical characteristics of the molecular crystals were obtained and compared with the sublimation and structural parameters. Solubility and solvation processes of 1,2,4-thiadiazoles in buffer, n -hexane and n -octanol were studied within the wide range of temperature intervals and thermodynamic functions were calculated. Specific and nonspecific interactions of molecules resolved in crystals and solvents were estimated and compared. Distribution processes of compounds in buffer/n -octanol and buffer/n -hexane systems (describing different types of membranes) were investigated. Analysis of transfer processes of studied molecules from the buffer to n -octanol/n -hexane phases was carried out by the diagram method with evaluation of the enthalpic and entropic terms. This approach allows us to design drug molecules with optimal passive transport properties. Calcium-blocking properties of the substances were evaluated. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3754,3768, 2010 [source] Extent and mechanism of solvation and partitioning of isomers of substituted benzoic acids: A thermodynamic study in the solid state and in solutionJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2008German L. Perlovich Abstract Temperature dependency of saturated vapour pressure and thermochemical characteristics of fusion processes for 2-, 3- and 4-methoxybenzoic acids (anisic acids) were measured and thermodynamic functions of sublimation, fusion, and evaporation calculated. A new approach to split specific and nonspecific energetic terms in the crystal lattice was developed. For methoxybenzoic acid isomers as well as for a number of analogous molecules, a parameter describing molecular packing density by the ratio of free volume of the molecules in the crystal lattice and van der Waals molecular volume is defined. Its relationship to Gibbs energy of sublimation and to the respective melting points was analysed. Temperature dependencies of solubility in buffers with pH 2.0 and 7.4, n -octanol and n -hexane were measured. The thermodynamic functions of solubility, solvation and transfer processes were deduced. Concentration dependence of partition coefficients for the outlined isomers was measured. Specific and nonspecific solvation terms were distinguished using the transfer from the ,inert' n -hexane to the other solvents. Comparison analysis of specific and nonspecific interactions in the solid state and in solution was carried out. A diagram enabling analysis of the mechanism of the partitioning process was applied. It was found that position of substituents essentially affects the mechanism of partitioning in buffer pH 2.0, however, at pH 7.4, the mechanism is independent of the position of the substituent. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:3883,3896, 2008 [source] The effects of surface lactone hydrolysis and temperature on the specific and nonspecific interactions between phenobarbital and activated carbon surfacesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2006Dale Eric Wurster Abstract The effect of hydrolyzing lactone functional groups on the surfaces of different activated carbons upon the specific and nonspecific interactions between phenobarbital and activated carbon surfaces was studied. The effect of temperature on both specific and nonspecific interactions was also studied. The increase in OH groups on the surfaces of activated carbons, as a result of hydrolyzing surface lactone groups, caused an increase in the specific adsorption capacity (K2) for phenobarbital without having a significant effect on the hydrophobic bonding capacity (KHB). Increasing the temperature at which the adsorption experiment was carried out, on the other hand, resulted in a decrease in KHB without having a significant effect on K2. The decrease in KHB per unit temperature increase was the same regardless of the activated carbon. These results are in very good agreement with the modified-Langmuir-like equation (M-LLE). © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95: 1540,1548, 2006 [source] Virus filtration of high-concentration monoclonal antibody solutionsBIOTECHNOLOGY PROGRESS, Issue 2 2009Bruno F. Marques Abstract The ability to process high-concentration monoclonal antibody solutions (> 10 g/L) through small-pore membranes typically used for virus removal can improve current antibody purification processes by eliminating the need for feed stream dilution, and by reducing filter area, cycle-time, and costs. In this work, we present the screening of virus filters of varying configurations and materials of construction using MAb solutions with a concentration range of 4,20 g/L. For our MAbs of interest,two different humanized IgG1s,flux decay was not observed up to a filter loading of 200 L/m2 with a regenerated cellulose hollow fiber virus removal filter. In contrast, PVDF and PES flat sheet disc membranes were plugged by solutions of these same MAbs with concentrations >4 g/L well before 50 L/m2. These results were obtained with purified feed streams containing <2% aggregates, as measured by size exclusion chromatography, where the majority of the aggregate likely was composed of dimers. Differences in filtration flux performance between the two MAbs under similar operating conditions indicate the sensitivity of the system to small differences in protein structure, presumably due to the impact of these differences on nonspecific interactions between the protein and the membrane; these differences cannot be anticipated based on protein pI alone. Virus clearance data with two model viruses (XMuLV and MMV) confirm the ability of hollow fiber membranes with 19 ± 2 nm pore size to achieve at least 3,4 LRV, independent of MAb concentration, over the range examined. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 [source] A Macrophage Cell Model for Selective Metalloproteinase Inhibitor DesignCHEMBIOCHEM, Issue 13 2008Faith E. Jacobsen Abstract The desire to inhibit zinc-dependent matrix metalloproteinases (MMPs) has, over the course of the last 30 years, led to the development of a plethora of MMP inhibitors that bind directly to the active-site metal. With one exception, all of these drugs have failed in clinical trials, due to many factors, including an apparent lack of specificity for MMPs. To address the question of whether these inhibitors are selective for MMPs in a biological setting, a cell-based screening method is presented to compare the relative activities of zinc, heme iron, and non-heme iron enzymes in the presence of these compounds using the RAW264.7 macrophage cell line. We screened nine different zinc-binding groups (ZBGs), four established MMP inhibitors (MMPis), and two novel MMP inhibitors developed in our laboratory to determine their selectivities against five different metalloenzymes. Using this model, we identified two nitrogen donor compounds,2,2,-dipyridylamine (DPA) and triazacyclononane (TACN),as the most selective ZBGs for zinc metalloenzyme inhibitor development. We also demonstrated that the model could predict known nonspecific interactions of some of the most commonly used MMPis, and could also give cross-reactivity information for newly developed MMPis. This work demonstrates the utility of cell-based assays in both the design and the screening of novel metalloenzyme inhibitors. [source] |