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https://www.readbyqxmd.com/read/28731685/lipophilic-polycation-vehicles-display-high-plasmid-dna-delivery-to-multiple-cell-types
#1
Yaoying Wu, Adam E Smith, Theresa M Reineke
A class of cationic poly(alkylamidoamine)s (PAAAs) containing lipophilic methylene linkers were designed and examined as in vitro plasmid DNA (pDNA) delivery agents. The PAAAs were synthesized via step-growth polymerization between a diamine monomer and each of four different diacid chloride monomers with varying methylene linker lengths, including glutaryl chloride, adipoyl chloride, pimeloyl chloride, and suberoyl chloride, which served to systematically increase the lipophilicity of the polymers. The synthesized polymers successfully complexed with pDNA in reduced serum medium at N/P ratios of 5 and greater, resulting in polyplexes with hydrodynamic diameters of approximately 1 μm...
July 21, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28731341/a-2d-coordination-network-that-detects-nitro-explosives-in-water-catalyzes-baylis-hillman-reactions-and-undergoes-unusual-2d%C3%A2-3d-single-crystal-to-single-crystal-transformation
#2
Vivekanand Sharma, Dinesh De, Sanchari Pal, Prithwidip Saha, Parimal K Bharadwaj
The solvothermal reaction of Zn(NO3)2·6H2O and a linear dicarboxylate ligand H2L, in the presence of urotropine in N,N'-dimethylformamide (DMF), gives rise to a new porous two-dimensional (2D) coordination network, {[Zn3(L)3(urotropine)2]·2DMF·3H2O}n (1), with hxl topology. Interestingly, framework 1 exhibits excellent emission properties owing to the presence of naphthalene moiety in the linker H2L, that can be efficiently suppressed by subtle quantity of nitro explosives in aqueous medium. Furthermore, presence of urotropine molecules bound to the metal centers, 1 is found to be an excellent heterogeneous catalyst meant for atom-economical C-C bond-forming Baylis-Hillman reactions...
July 21, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28731301/lead-ii-complexes-of-amino-acids-peptides-and-other-related-ligands-of-biological-interest
#3
Etelka Farkas, Péter Buglyó
Lead(II) forms (NH2,COO-)-chelated mono- and bis-complexes with simple amino acids, while mono-complexes with pH-dependent coordination modes exist with simple dipeptides. These mostly hemidirected complexes have moderate stability. While a weak interaction of side chain imidazole and carboxylate in lead(II)-aminoacidato complexes is found, the thiolate group has an exceptionally high affinity to this metal ion. For example, tridentate (NH2,COO-,S-)-coordination of penicillamine (Pen) and cysteine (Cys) results in an extremely strong interaction with lead(II), but, owing to the sterical effect of the 6s2 pair, a second ligand is not able to coordinate in the above mentioned tridentate way...
April 10, 2017: Metal Ions in Life Sciences
https://www.readbyqxmd.com/read/28730430/computational-generation-of-rna-nanorings
#4
Rishabh Sharan, Eckart Bindewald, Wojciech K Kasprzak, Bruce A Shapiro
A variety of designed RNA ring structures (ranging from triangles to hexagonal rings) have been reported in the scientific literature. Designing self-assembling RNA ring structures from structural motifs is, however, a nontrivial problem as there are many combinations of motifs and linking helices. Moreover, most combinations of motifs and linker helices will not lead to ring closure. A solution to this problem was recently published using a "design-by-catalog" approach where motif combinations that lead to rings are precomputed and tabulated...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28728108/new-tacrine-dimers-with-antioxidant-linkers-as-dual-drugs-anti-alzheimer-s-and-antiproliferative-agents
#5
Jesús M Roldán-Peña, Daniel Alejandre-Ramos, Óscar López, Inés Maya, Irene Lagunes, José M Padrón, Luis Emiliano Peña-Altamira, Manuela Bartolini, Barbara Monti, Maria L Bolognesi, José G Fernández-Bolaños
We have designed a series of tacrine-based homo- and heterodimers that incorporate an antioxidant tether (selenoureido, chalcogenide) as new dual compounds: for the treatment of Alzheimer's disease and as antiproliferative agents. Symmetrical homodimers bearing a dichalcogenide or selenide-based tether, the best compounds in the series, were found to be strong and highly selective electric eel AChE inhibitors, with inhibition constants within the low nanomolar range. This high inhibitory activity was confirmed on recombinant human AChE for the most interesting derivatives...
June 27, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28728105/discovery-of-imidazopyridines-containing-isoindoline-1-3-dione-framework-as-a-new-class-of-bace1-inhibitors-design-synthesis-and-sar-analysis
#6
Sara Azimi, Afsaneh Zonouzi, Omidreza Firuzi, Aida Iraji, Mina Saeedi, Mohammad Mahdavi, Najmeh Edraki
Alzheimer's disease is characterized by chronic neurodegeneration leading to dementia. The main cause of neurodegeneration is considered to be the accumulation of amyloid-β. Inhibiting BACE1 is a well-studied approach to lower the burden of amyloid-β aggregates. We designed a series of imidazopyridines-based compounds bearing phthalimide moieties as inhibitors of BACE1. The compounds 8a-o were synthesized by the Groebke-Blackburn-Bienaymé three-component reaction of heteroaromatic amidines, aldehydes and isocyanides...
June 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28727178/tailored-band-gaps-in-sulphur-and-nitrogen-containing-porous-donor-acceptor-polymers-snps
#7
Dana Schwarz, Yaroslav S Kochergin, Amitava Acharja, Arun Ichangi, Maksym V Opanasenko, Jiří Čejka, Uwe Lappan, Pal Arki, Junjie He, Johannes Schmidt, Petr Nachtigall, Arne Thomas, Michael Janus Bojdys
Donor-acceptor dyads hold the key to tuning of electrochemical properties and enhanced mobility of charge carriers, yet their incorporation into a heterogeneous polymer network proves difficulty due to the fundamentally different chemistry of the donor- and acceptor-subunits. We present a family of sulphur and nitrogen containing porous polymers (SNPs) that are obtained via Sonogashira-Hagihara cross-coupling and that combine electron-withdrawing triazine (C3N3) and electron donating, sulphur-containing linkers...
July 20, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28726672/the-influence-of-surface-potential-on-the-optical-switching-of-spiropyran-self-assembled-monolayers
#8
Tobias Garling, Yujin Tong, Tamim Darwish, Martin Wolf, R Kramer Campen
Surfaces whose macroscopic properties can be switched by light are potentially useful in a wide variety of applications. One such promising application is electrochemical sensors that can be gated by optically switching the electrode <i>on</i> or <i>off</i>. One way to make such a switchable electrode is by depositing a self-assembled monolayer of bistable, optically switchable molecules onto an electrode surface. Quantitative application of any such sensor requires understanding how changes in interfacial field affect the composition of photostationary states, <i>i...
July 20, 2017: Journal of Physics. Condensed Matter: An Institute of Physics Journal
https://www.readbyqxmd.com/read/28726003/chitooligosaccharides-modified-reduction-sensitive-liposomes-enhanced-cytoplasmic-drug-delivery-and-osteosarcomas-tumor-inhibition-in-animal-models
#9
Xuelei Yin, Yingying Chi, Chuanyou Guo, Shuaishuai Feng, Jinhu Liu, Kaoxiang Sun, Zimei Wu
PURPOSE: To investigate the potential of a reduction-sensitive and fusogenic liposomes, enabled by surface-coating with chotooligosaccharides (COS) via a disulfide linker, for tumor-targeted cytoplasmic drug delivery. METHODS: COS (MW2000-5000) were chemically tethered onto the liposomes through a disulfide linker (-SS-) to cholesterol (Chol). Doxorubicin (DOX) was actively loaded in the liposomes. Their reduction-sensitivities, cellular uptake, cytotoxicity, pharmacokinetics and antitumor efficacy were investigated...
July 19, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28725972/the-versatility-of-n-alkyl-methoxyamine-bi-functional-linkers-for-the-preparation-of-glycoconjugates
#10
Stefan Munneke, Emma M Dangerfield, Bridget L Stocker, Mattie S M Timmer
The application of N-glycosyl-N-alkyl-methoxyamine bi-functional linkers for the synthesis of a variety of glycoconjugates is described. The linker contains a specific functional group, such as an amine, azide, thiol, or carboxylic acid, which can be used for conjugation methodologies that include amide ligation, sulfonylation, copper-mediated Huisgen cycloaddition or thiol-maleimide coupling. In this way, glycoconjugates equipped with biotin, a fluorescent reporter, or a protein were efficiently synthesised, thus demonstrating the versatility of this type of oxyamine linker for the construction of glycoconjugate probes...
July 19, 2017: Glycoconjugate Journal
https://www.readbyqxmd.com/read/28724767/integrity-of-the-linker-of-nucleoskeleton-and-cytoskeleton-is-required-for-efficient-herpesvirus-nuclear-egress
#11
Barbara G Klupp, Teresa Hellberg, Harald Granzow, Kati Franzke, Beatriz Dominguez Gonzalez, Rose Goodchild, Thomas C Mettenleiter
Herpesvirus capsids assemble in the nucleus while final virion maturation proceeds in the cytoplasm. This requires that newly formed nucleocapsids cross the nuclear envelope (NE), which occurs by budding at the inner nuclear membrane (INM), release of the primary enveloped virion into the perinuclear space (PNS), and subsequent rapid fusion with the outer nuclear membrane (ONM). During this process the NE remains intact, even at late stages of infection. In addition, the spacing between the INM and ONM is maintained, as is that between the primary virion envelope and nuclear membranes...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28724261/development-of-a-sandwich-enzyme-linked-immunosorbent-assay-for-dtmp-gh-fusion-protein-by-rational-immunogen-selection
#12
Song Wang, Mingqiang Shen, Shilei Chen, Cheng Wang, Fang Chen, Mo Chen, Gaomei Zhao, Xinze Ran, Tianmin Cheng, Yongping Su, Yang Xu, Junping Wang
dTMP-GH is a chimeric protein containing a tandem dimer of thrombopoietin mimetic peptide (dTMP) fused to human growth hormone (hGH) prepared previously by our team. It shows significant bioactivity in promoting thrombocytopoiesis, but detection of intact dTMP-GH in plasma is still a challenge due to the presence of endogenous hGH. In this study, a rabbit polyclonal antibody with high affinity to dTMP was obtained with a BSA-conjugated immunogen composed of 20 amino acids sequence spanning two TMP and the linker...
December 2017: AMB Express
https://www.readbyqxmd.com/read/28722423/generation-of-a-cgmp-indicator-with-an-expanded-dynamic-range-by-optimization-of-amino-acid-linkers-between-a-fluorescent-protein-and-pde5%C3%AE
#13
Shogo Matsuda, Kazuki Harada, Motoki Ito, Mai Takizawa, Devina Wongso, Takashi Tsuboi, Tetsuya Kitaguchi
Here we describe the development of a single fluorescent protein (FP)-based cGMP indicator, Green cGull, based on the cGMP binding domain from mouse phosphodiesterase 5α. The dynamic range of Green cGull was enhanced to a 7.5-fold fluorescence change upon cGMP binding by optimization of the amino acid linkers between the cGMP binding domain and FP. Green cGull has excitation and emission peaks at 498 and 522 nm, respectively, and specifically responds to cGMP in a dose-dependent manner. Live cell imaging analysis revealed that addition of a nitric oxide (NO) donor induced different cGMP kinetics and was cell-type dependent...
January 27, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28722010/a-shape-shifting-redox-foldase-contributes-to-proteus-mirabilis-copper-resistance
#14
Emily J Furlong, Alvin W Lo, Fabian Kurth, Lakshmanane Premkumar, Makrina Totsika, Maud E S Achard, Maria A Halili, Begoña Heras, Andrew E Whitten, Hassanul G Choudhury, Mark A Schembri, Jennifer L Martin
Copper resistance is a key virulence trait of the uropathogen Proteus mirabilis. Here we show that P. mirabilis ScsC (PmScsC) contributes to this defence mechanism by enabling swarming in the presence of copper. We also demonstrate that PmScsC is a thioredoxin-like disulfide isomerase but, unlike other characterized proteins in this family, it is trimeric. PmScsC trimerization and its active site cysteine are required for wild-type swarming activity in the presence of copper. Moreover, PmScsC exhibits unprecedented motion as a consequence of a shape-shifting motif linking the catalytic and trimerization domains...
July 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28721592/construction-purification-and-characterization-of-a-homodimeric-granulocyte-colony-stimulating-factor
#15
Gitana Mickiene, Indre Dalgediene, Zilvinas Dapkunas, Gintautas Zvirblis, Henrikas Pesliakas, Algirdas Kaupinis, Mindaugas Valius, Edita Mistiniene, Milda Pleckaityte
Granulocyte colony-stimulating factor (G-CSF) has found widespread clinical application, and modified forms with improved biopharmaceutical properties have been marketed as well. PEGylation, the covalent modification of G-CSF with polyethylene glycol (PEG), has a beneficial effect on drug properties, but there are concerns connected to the immunogenicity of PEGylated compounds and bioaccumulation of the synthetic polymer. To overcome challenges connected with chemical modifications, we developed fusion proteins composed of two G-CSF molecules connected via different peptide linkers...
July 18, 2017: Molecular Biotechnology
https://www.readbyqxmd.com/read/28720589/dynamic-role-of-the-tether-helix-in-pip2-dependent-gating-of-a-g-protein-gated-potassium-channel
#16
Emre Lacin, Prafulla Aryal, Ian W Glaaser, Karthik Bodhinathan, Eric Tsai, Nidaa Marsh, Stephen J Tucker, Mark S P Sansom, Paul A Slesinger
G protein-gated inwardly rectifying potassium (GIRK) channels control neuronal excitability in the brain and are implicated in several different neurological diseases. The anionic phospholipid phosphatidylinositol 4,5 bisphosphate (PIP2) is an essential cofactor for GIRK channel gating, but the precise mechanism by which PIP2 opens GIRK channels remains poorly understood. Previous structural studies have revealed several highly conserved, positively charged residues in the "tether helix" (C-linker) that interact with the negatively charged PIP2 However, these crystal structures of neuronal GIRK channels in complex with PIP2 provide only snapshots of PIP2's interaction with the channel and thus lack details about the gating transitions triggered by PIP2 binding...
July 18, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28720505/chemically-generated-igg2-bispecific-antibodies-through-disulfide-bridging
#17
James T Patterson, Edwige Gros, Heyue Zhou, Ghazi Atassi, Lisa Kerwin, Lisa Carmody, Tong Zhu, Bryan Jones, Yanwen Fu, Gunnar F Kaufmann
Bispecific antibodies (BsAbs) are designed to engage two antigens simultaneously, thus, effectively expanding the ability of antibody-based therapeutics to target multiple pathways within the same cell, engage two separate soluble antigens, bind the same antigen with distinct paratopes, or crosslink two different cell types. Many recombinant BsAb formats have emerged, however, expression and purification of such constructs can often be challenging. To this end, we have developed a chemical strategy for generating BsAbs using native IgG2 architecture...
July 8, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28719949/seroprevalence-of-toxoplasmosis-with-elisa-and-rapid-diagnostic-test-among-residents-in-gyodong-do-inchon-city-korea-a-four-year-follow-up
#18
Yeong Hoon Kim, Ji Hoo Lee, Seong Kyu Ahn, Tong-Soo Kim, Sung-Jong Hong, Chom-Kyu Chong, Hye-Jin Ahn, Ho-Woo Nam
ELISA has been used for the diagnosis of toxoplasmosis, but it is being gradually replaced by a rapid diagnostic test (RDT). We compared and analyzed ELISA and RDT results using the sera collected during 4 consecutive years from residents of Gyodong-do (Island), Incheon-city, Korea. Sera from 921, 993, 940, and 838 adult residents were collected on a yearly basis (2010-2013). ELISA was performed by using a crude extract of T. gondii RH strain antigen and IgG/IgM RDT mounted with recombinant fragment of major surface antigen (SAG1), GST-linker-SAG1A, were applied to the sera...
June 2017: Korean Journal of Parasitology
https://www.readbyqxmd.com/read/28719648/oligo-ethylene-glycol-sidechain-microgels-prepared-in-absence-of-cross-linking-agent-polymerization-characterization-and-variation-of-particle-deformability
#19
Nicole Welsch, L Andrew Lyon
We present a systematic study of self-cross-linked microgels formed by precipitation polymerization of oligo ethylene glycol methacrylates. The cross-linking density of these microgels and, thus, the network flexibility can be easily tuned through the modulation of the reaction temperature during polymerization. Microgels prepared in absence of any difunctional monomer, i.e. cross-linker, show enhanced deformability and particle spreading on solid surfaces as compared to microgels cross-linked with varying amounts of poly(ethylene glycol diacrylate) (PEG-DA) in addition to self-crosslinking...
2017: PloS One
https://www.readbyqxmd.com/read/28719188/phage-selection-of-cyclic-peptides-for-application-in-research-and-drug-development
#20
Kaycie Deyle, Xu-Dong Kong, Christian Heinis
Cyclic peptides can bind to protein targets with high affinities and selectivities, which makes them an attractive modality for the development of research reagents and therapeutics. Additional properties, including low inherent toxicity, efficient chemical synthesis, and facile modification with labels or immobilization reagents, increase their attractiveness. Cyclic peptide ligands against a wide range of protein targets have been isolated from natural sources such as bacteria, fungi, plants, and animals...
July 18, 2017: Accounts of Chemical Research
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