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排序方式: 共有2393条查询结果,搜索用时 31 毫秒
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Dr. Blijke S. Kroezen Gabriele Conti Benedetta Girardi Dr. Jonathan Cramer Dr. Xiaohua Jiang Dr. Said Rabbani Jennifer Müller Maja Kokot Enrico Luisoni Prof. Daniel Ricklin Dr. Oliver Schwardt Prof. Beat Ernst 《ChemMedChem》2020,15(18):1706-1719
Siglecs are members of the immunoglobulin gene family containing sialic acid binding N-terminal domains. Among them, Siglec-8 is expressed on various cell types of the immune system such as eosinophils, mast cells and weakly on basophils. Cross-linking of Siglec-8 with monoclonal antibodies triggers apoptosis in eosinophils and inhibits degranulation of mast cells, making Siglec-8 a promising target for the treatment of eosinophil- and mast cell-associated diseases such as asthma. The tetrasaccharide 6’-sulfo-sialyl Lewisx has been identified as a specific Siglec-8 ligand in glycan array screening. Here, we describe an extended study enlightening the pharmacophores of 6’-sulfo-sialyl Lewisx and the successful development of a high-affinity mimetic. Retaining the neuraminic acid core, the introduction of a carbocyclic mimetic of the Gal moiety and a sulfonamide substituent in the 9-position gave a 20-fold improved binding affinity. Finally, the residence time, which usually is the Achilles tendon of carbohydrate/lectin interactions, could be improved. 相似文献
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Jasmin Kuhn Philipp M. Klein Nader Al Danaf Joel Z. Nordin Sren Reinhard Dominik M. Loy Miriam Hhn Samir El Andaloussi Don C. Lamb Ernst Wagner Yoshitsugu Aoki Taavi Lehto Ulrich Lchelt 《Advanced functional materials》2019,29(48)
Phosphorodiamidate morpholino oligomers (PMOs) are oligonucleotide analogs that can be used for therapeutic modulation of pre‐mRNA splicing. Similar to other classes of nucleic acid‐based therapeutics, PMOs require delivery systems for efficient transport to the intracellular target sites. Here, artificial peptides based on the oligo(ethylenamino) acid succinyl‐tetraethylenpentamine (Stp), hydrophobic modifications, and an azide group are presented, which are used for strain‐promoted azide‐alkyne cycloaddition conjugation with splice‐switching PMOs. By systematically varying the lead structure and formulation, it is determined that the type of contained fatty acid and supramolecular assembly have a critical impact on the delivery efficacy. A compound containing linolenic acid with three cis double bonds exhibits the highest splice‐switching activity and significantly increases functional protein expression in pLuc/705 reporter cells in vitro and after local administration in vivo. Structural and mechanistic studies reveal that the lipopeptide PMO conjugates form nanoparticles, which accelerate cellular uptake and that the content of unsaturated fatty acids enhances endosomal escape. In an in vitro Duchenne muscular dystrophy exon skipping model using H2K‐mdx52 dystrophic skeletal myotubes, the highly potent PMO conjugates mediate significant splice‐switching at very low nanomolar concentrations. The presented aminoethylene‐lipopeptides are thus a promising platform for the generation of PMO‐therapeutics with a favorable activity/toxicity profile. 相似文献
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High‐performance thermosets with tailored properties derived from methacrylated eugenol and epoxy‐based vinyl ester 下载免费PDF全文
Yuehong Zhang Yuzhan Li Vijay Kumar Thakur Zhenhua Gao Jiyou Gu Michael R Kessler 《Polymer International》2018,67(5):544-549
A renewable chemical, eugenol, is methacrylated to produce methacrylated eugenol (ME) employing the Steglich esterification reaction without any solvent. The resulting ME is used as a low‐viscosity co‐monomer to replace styrene in a commercial epoxy‐based vinyl ester resin (VE). The volatility and viscosity of ME and styrene are compared. The effect of ME loading and temperature on the viscosity of the VE–ME resin is investigated. Moreover, the thermomechanical properties, curing extent and thermal stability of the fully cured VE–ME thermosets are systematically examined. The results indicate that ME is a monomer with low volatility and low viscosity, and therefore the incorporation of ME monomer in VE resins allows significant reduction of viscosity. Moreover, the viscosity of the VE–ME resin can be tailored by adjusting the ME loadings and processing temperature to meet commercial liquid molding technology requirements. The glass transition temperatures of VE–ME thermosets range from 139 to 199 °C. In addition, more than 95% of the monomer is incorporated and fixed in the crosslinked network structure of VE–ME thermosets. Overall, the developed ME monomer exhibits promising potential for replacing styrene as an effective low‐viscosity co‐monomer. The VE–ME resins show great advantages for use in polymer matrices for high‐performance fiber‐reinforced composites. This work is of great significance to the vinyl ester industry by providing detailed experimental support. © 2018 Society of Chemical Industry 相似文献
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爱立信IMS weShare业务有20%的开发与用户视觉体验相关(用户界面、图标、标签以及进度条),其它的80%则主要致力于设备间的系统.与此相对比,用户的体验则完全(100%)有赖于其可接触的事物. 相似文献
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BACKGROUND & AIMS: The molecular mechanisms underlying pancreatitis are largely unknown. The goal of this study was to identify an early genetic event that correlated with pancreatitis. METHODS: Differential display of messenger RNAs (mRNAs) was conducted on normal pancreas vs. those of animals with secretagogue-induced pancreatitis. Northern blots from normal animals and animals with experimental acute pancreatitis were probed with cloned complementary DNAs for chemokines. Pancreatitis was induced with cerulein and by retrograde injection of bile salts. Immunocytochemistry was used to identify the source of chemokine expression. Pyrrolidine dithiocarbamate was tested for effects on chemokine expression and pancreatitis. RESULTS: A differentially amplified band was consistently observed early after cerulein hyperstimulation. This band was identified as a portion of the mob-1 gene, an alpha-chemokine. Northern analysis indicated that mRNAs for mob-1 and another chemokine, mcp-1, were induced after cerulein hyperstimulation in vivo. mob-1 mRNA was also induced by retrograde injection of bile salts and by cerulein in acinar cells in vitro. mob-1 protein was localized to exocrine cells in pancreata of diseased animals. Pyrrolidine dithiocarbamate inhibited both chemokine gene expression and early inflammatory characteristics of pancreatitis. CONCLUSIONS: Chemokines are induced in acinar cells by treatments that induce pancreatitis and may play an important role in the early stages of the disease. 相似文献
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The electrochemical faceting of polycrystalline (pc) platinum yielding a (100)-preferred oriented electrode surface was accomplished in HF solutions by applying to the pc platinum electrode a square wave potential perturbation at 1 kHz in the 0.2 to 1.3 V range (vs rhe). SEM patterns of the resulting surfaces were also obtained. For HF concentrations up to 2 M no appreciable influence of the electrolyte concentration on the electrochemical faceting was noticed. Otherwise, the voltammetric response of the (100)-type preferred oriented platinum surface in the H-adatom potential range when compared to previously reported data resulted remarkably sensitive to the electrolyte composition. The discussion of results was based on the non-equilibrium adsorption conditions for anions under the periodic perturbation. 相似文献