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171.
Five copper(I) complexes having general formula [Cu2(μ-X)2(κ2-P,P-B-dppf)2] (X = Cl(1), Br(2), I(3), CN(4), and SCN(5)) were prepared starting with CuX and B-dppf in 1:1 molar ratio in DCM-MeOH (50:50 V/V) at room temperature. The complexes have been characterized by elemental analyses, IR, 1H NMR, 31P NMR and electronic spectral studies. Molecular structures for 1, 2 and 4 were determined crystallographically. Complexes 1, 2 and 4 exist as centrosymmetric dimers in which the two copper atoms are bonded to two bridging B-dppf ligands and two bridging (pseudo-)halide groups in a μ-η1 bonding mode to generate nearly planar Cu2(μ-η1-X)2 framework. Both bridging B-dppf ligands are arranged in antiperiplanar staggered conformation in 1 and 2 (mean value 56.40-56.76°), and twisted from the eclipsed conformation (mean value 78.19°) in 4. The Φ angle value in 4 is relatively larger as compared to 1 and 2. This seems to indicate that the molecular core [Cu2(μ-η1-X)2] in 4 is a sterically demanding system that forces the B-dppf ligand to adopt a relatively strained conformation in comparison to less strained system in 1 and 2. All the complexes exhibit moderately strong luminescence properties in the solution state at ambient temperature. 相似文献
172.
Despite advances against infectious diseases over the past century, Neisseria meningitidis remains a major causative agent of meningitis and septicaemia worldwide. Its adaptation for survival in the human nasopharynx makes the meningococcus a highly successful commensal bacterium. Recent progress has been made in understanding the mechanisms that enable neisserial colonisation, in terms of the role of type IV pili, the impact of other adhesins, biofilm formation, nutrient acquisition and resistance to host immune defences. Refinements in cell-based and in vivo models will lead to improved understanding of the colonisation process, and hopefully to more effective vaccines and therapeutic strategies. 相似文献
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175.
Vogeley L Trivedi VD Sineshchekov OA Spudich EN Spudich JL Luecke H 《Journal of molecular biology》2007,367(3):741-751
We present crystal structures of the Anabaena sensory rhodopsin transducer (ASRT), a soluble cytoplasmic protein that interacts with the first structurally characterized eubacterial retinylidene photoreceptor Anabaena sensory rhodopsin (ASR). Four crystal structures of ASRT from three different spacegroups were obtained, in all of which ASRT is present as a planar (C4) tetramer, consistent with our characterization of ASRT as a tetramer in solution. The ASRT tetramer is tightly packed, with large interfaces where the well-structured beta-sandwich portion of the monomers provides the bulk of the tetramer-forming interactions, and forms a flat, stable surface on one side of the tetramer (the beta-face). Only one of our four different ASRT crystals reveals a C-terminal alpha-helix in the otherwise all-beta protein, together with a large loop from each monomer on the opposite face of the tetramer (the alpha-face), which is flexible and largely disordered in the other three crystal forms. Gel-filtration chromatography demonstrated that ASRT forms stable tetramers in solution and isothermal microcalorimetry showed that the ASRT tetramer binds to ASR with a stoichiometry of one ASRT tetramer per one ASR photoreceptor with a K(d) of 8 microM in the highest affinity measurements. Possible mechanisms for the interaction of this transducer tetramer with the ASR photoreceptor via its flexible alpha-face to mediate transduction of the light signal are discussed. 相似文献
176.
Recently we have demonstrated that replacing His(6) by constrained amino acids(2) in the well-known antagonist SHU-9119 resulted in potent and selective antagonist ligands especially at the hMC3R and hMC5 receptors. With the aim to further explore position 6 in the sequence of SHU-9119 and MT-II, we have designed, synthesized, and pharmacologically characterized a series of peptide analogues of MT-II and SHU-9119 at the human melanocortin receptors subtypes MC3R, MC4R and MC5R. All these peptides were modified at position 6 with constrained amino acids which are commercially available. In this study, we have identified new selective ligands for the hMC4R, and an antagonist for the hMC3/hMC4 receptors. Additionally, we have discovered an interesting new selective antagonist at the hMC3R, Ac-Nle-c[Asp-betaAla-DNal(2')-Arg-Trp-Lys]-NH(2) (2, PG-106) which represents an important tool in further biological investigations of the hMC3R. PG-106 will be useful in further efforts to differentiate the substructural features responsible for selectivity at the hMC3R, hMC4R, and hMC5R. 相似文献
177.
Summary A tropical white-rot basidiomycete, BDT-14 (DSM 15396) was investigated for its chromium (VI) biosorption potential from an
aqueous solution. Pre-treatment of fungal biomass with acid resulted in 100% metal adsorption compared to only 26.64% adsorption
without any pre-treatment. Chromium adsorption was a rapid process at early exposure resulting in 60% chromium removal within
the first 2 h of exposure. An increase in biomass showed an increase in the total metal ions adsorption but a decrease in
specific uptake of metal ions. The concentrations of chromium had a pronounced effect on the rate of adsorption. The adsorption
efficiency was 100% when the initial Cr (VI) concentration was 100 mg l−1 with 1,000 mg biomass. Only 47.5% adsorption was observed with 500 mg l−1 Cr (VI) concentration. The adsorption data fit well with the Langmuir and Freundlich isotherm models. Comprehensive characterization
of parameters indicates BDT−14 biomass as a promising material for Cr (VI) adsorption. 相似文献
178.
Pfefferkorn JA Song Y Sun KL Miller SR Trivedi BK Choi C Sorenson RJ Bratton LD Unangst PC Larsen SD Poel TJ Cheng XM Lee C Erasga N Auerbach B Askew V Dillon L Hanselman JC Lin Z Lu G Robertson A Olsen K Mertz T Sekerke C Pavlovsky A Harris MS Bainbridge G Caspers N Chen H Eberstadt M 《Bioorganic & medicinal chemistry letters》2007,17(16):4538-4544
179.
Bratton LD Auerbach B Choi C Dillon L Hanselman JC Larsen SD Lu G Olsen K Pfefferkorn JA Robertson A Sekerke C Trivedi BK Unangst PC 《Bioorganic & medicinal chemistry》2007,15(16):5576-5589
In an effort to identify hepatoselective inhibitors of HMG-CoA reductase, two series of pyrroles were synthesized and evaluated. Efforts were made to modify (3R,5R)-7-[3-(4-fluorophenyl)-1-isopropyl-4-phenyl-5-phenylcarbamoyl-1H-pyrrol-2-yl]-3,5-dihydroxy-heptanoic acid sodium salt 30 in order to reduce its lipophilicity and therefore increase hepatoselectivity. Two strategies that were explored were replacement of the lipophilic 3-phenyl substituent with either a polar function (pyridyl series) or with lower alkyl substituents (lower alkyl series) and attachment of additional polar moieties at the 2-position of the pyrrole ring. One compound was identified to be both highly hepatoselective and active in vivo. We report the discovery, synthesis, and optimization of substituted pyrrole-based hepatoselective ligands as potent inhibitors of HMG-CoA reductase for reducing low density lipoprotein cholesterol (LDL-c) in the treatment of hypercholesterolemia. 相似文献
180.
Steven Johnson Lionel Tan Stijn van der Veen Joseph Caesar Elena Goicoechea De Jorge Rachel J. Harding Xilian Bai Rachel M. Exley Philip N. Ward Nicola Ruivo Kaushali Trivedi Elspeth Cumber Rhian Jones Luke Newham David Staunton Rafael Ufret-Vincenty Ray Borrow Matthew C. Pickering Susan M. Lea Christoph M. Tang 《PLoS pathogens》2012,8(10)
Neisseria meningitis remains a leading cause of sepsis and meningitis, and vaccines are required to prevent infections by this important human pathogen. Factor H binding protein (fHbp) is a key antigen that elicits protective immunity against the meningococcus and recruits the host complement regulator, fH. As the high affinity interaction between fHbp and fH could impair immune responses, we sought to identify non-functional fHbps that could act as effective immunogens. This was achieved by alanine substitution of fHbps from all three variant groups (V1, V2 and V3 fHbp) of the protein; while some residues affected fH binding in each variant group, the distribution of key amino underlying the interaction with fH differed between the V1, V2 and V3 proteins. The atomic structure of V3 fHbp in complex with fH and of the C-terminal barrel of V2 fHbp provide explanations to the differences in the precise nature of their interactions with fH, and the instability of the V2 protein. To develop transgenic models to assess the efficacy of non-functional fHbps, we determined the structural basis of the low level of interaction between fHbp and murine fH; in addition to changes in amino acids in the fHbp binding site, murine fH has a distinct conformation compared with the human protein that would sterically inhibit binding to fHbp. Non-functional V1 fHbps were further characterised by binding and structural studies, and shown in non-transgenic and transgenic mice (expressing chimeric fH that binds fHbp and precisely regulates complement system) to retain their immunogenicity. Our findings provide a catalogue of non-functional fHbps from all variant groups that can be included in new generation meningococcal vaccines, and establish proof-in-principle for clinical studies to compare their efficacy with wild-type fHbps. 相似文献