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《MABS-AUSTIN》2013,5(6):503-504
The development of an immune response to a protein therapeutic may nullify its beneficial activity or result in adverse events. Immunogenicity is, therefore, a major concern for clinicians, regulatory authorities and the biopharmaceutical industry. These concerns are particularly acute for the treatment of chronic diseases, as opposed to cancer, that may require repeated exposure to therapeutic over extended cycles of remission/relapse. There are many parameters that may be contributory to immunogenicity; however, the “bête noire,” for the past decade has been aggregation.1-3 相似文献
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The chromium, manganese, and cobalt complexes of transferrin 总被引:4,自引:0,他引:4
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Burgmayer SJ Kim M Petit R Rothkopf A Kim A BelHamdounia S Hou Y Somogyi A Habel-Rodriguez D Williams A Kirk ML 《Journal of inorganic biochemistry》2007,101(11-12):1601-1616
The preparation and characterization of new model complexes for the molybdenum cofactor are reported. The new models are distinctive for the inclusion of pterin-substituted dithiolene chelates and have the formulation Tp(*)MoX(pterin-R-dithiolene) (Tp(*)=tris(3,5,-dimethylpyrazolyl)borate), X=O, S, R=aryl. Syntheses of Mo(4+) and (5+) complexes of two pterin-dithiolene derivatives as both oxo and sulfido compounds, and improved syntheses for pterinyl alkynes and [Et(4)N][Tp(*)Mo(IV)(S)S(4)] reagents are described. Characterization methods include electrospray ionization mass spectrometry, electrochemistry, infrared spectroscopy, electron paramagnetic resonance and magnetic circular dichroism. Cyclic voltammetry reveals that the Mo(5+/4+) reduction potential is intermediate between that for dithiolenes with electron-withdrawing substituents and simple dithiolates chelates. Electron paramagnetic resonance and magnetic circular dichroism of Mo(5+) complexes where X=O, R=aryl indicates that the molybdenum environment in the new models is electronically similar to that in Tp(*)MoO(benzenedithiolate). 相似文献
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The bleomycin-iron complexes with CO, NO, C2H5NC, OH-, N-3, CN-, and CH3NH2 were characterized by electronic, ESR, 1H-NMR, and M?ssbauer spectroscopies and the findings were compared with the corresponding hemoprotein complexes. The 1H-NMR and M?ssbauer features for the CO and C2H5NC adducts of the bleomycin-Fe(II) complex are consistent with an S = 0 ferrous assignment. The OH-, CH3NH2, and N-3 adducts of the bleomycin-Fe(III) complex show the ESR, 1H-NMR, and M?ssbauer spectra typical of a low-spin Fe(III). The unique M?ssbauer parameters of the bleomycin-Fe(II)-NO complex demonstrate mixing between the NO pi- and the Fe 3d-orbitals. The magnitude of the proton chemical shifts over +/- 50 ppm indicates a high-spin ferric type for the bleomycin-Fe(III)-CN complex. The M?ssbauer parameters (delta EQ = 0.89 and delta = 0.48 mm/s) of the CN- adduct differ substantially from those of typical low-spin hemoprotein-cyanide complexes. Except for the CN- adduct, the M?ssbauer and crystal field parameters of these bleomycin-iron complexes are similar to those of the corresponding hemoprotein complexes. 相似文献
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Structural analysis of septin 2, 6, and 7 complexes 总被引:1,自引:0,他引:1
Mammalian septins comprise a family of 13 genes that encode GTP-binding proteins. Specific combinations of septins can hetero-oligomerize and form filaments in vivo and in vitro, by mechanisms that are not understood. Using fluorescence resonance energy transfer, size exclusion chromatography, and multi-angle light scattering techniques, we have characterized the conformation of a complex of filamentous human septins, Sept2, Sept6, and Sept7. We now show that Sept6 and Sept7 interact through a parallel coiled-coil, and that Sept2 interacts with Sept6 through their C-terminal domains. We have also been able to produce soluble, stable individual septins that behave as rod-like monomers and dimers. Taken together, these observations suggest that polymerized filaments could be comprised of laterally arranged septin core subunits. 相似文献
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The absorption spectra of hematein-aluminium solutions have been recorded at various concentrations and pH values; the solutions were prepared using analytically pure hematein and potassium alum as aluminium source. In aqueous solution, four different hematein-aluminium complexes could be distinguished by absorption spectroscopy. In weakly acidic media we observed the violet 1:1 and 1:2 complexes HmAl (VII) and HmAl2(3) (VIII), and in strongly acidic solution the red 1:1 complex HmAl2 (IX). Whereas, in weakly alkaline solution the blue 1:1 complex HmAl0 (X) was detected. By change of the pH value the complexes were mutual interconverted. The dye complexes were characterized by their absorption spectra and molar extinction coefficients. We have stained HeLa cells with the complex solutions under different experimental conditions. In all cases the nuclear staining was intense whereas the staining of the cytoplasm was weak. The microspectra of the stained nuclei were recorded and compared with the absorption spectra of the complexes in solution. Thus it was possible to identify the bound dye species. After staining in acidic media, the cells were red to red-violet depending on the reaction conditions. The three cationic dye species VII, VIII, and IX were bound in varying amounts. After blueing in weakly acidic media or in water, only the violet dye complex VII was detected whereas, after blueing in weakly alkaline media, only the blue complex X has been observed. Enzymatic digestion experiments have shown that the dye complexes in the nuclei were bound to DNA while those in the cytoplasm and nucleoli were bound to RNA. The binding between the dye complexes and the nucleic acids is discussed. 相似文献
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Summary Analytically pure hematoxylin (Htx), penta-acetylhematoxylin (PAHtx), and hematein (Hm) were isolated and characterized by 1H-NMR spectroscopy. The VIS/UV spectra of Htx and Hm were recorded in MeOH and in H2O at various pH values. The molar extinction coefficients of the long wavelength absorption bands are reported. The pK
a value for the 1st acidic dissociation step of Hm has been determined from the pH dependency of the absorption spectra of Hm in aqueous buffer solutions. Finally, the absorption spectra are qualitatively discussed. 相似文献
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Nuclear pore complexes are large aqueous channels that penetrate the nuclear envelope, thereby connecting the nuclear interior with the cytoplasm. Until recently, these macromolecular complexes were viewed as static structures, the only function of which was to control the molecular trafficking between the two compartments. It has now become evident that this simplistic scenario is inaccurate and that nuclear pore complexes are highly dynamic multiprotein assemblies involved in diverse cellular processes ranging from the organization of the cytoskeleton to gene expression. In this review, we discuss the most recent developments in the nuclear-pore-complex field, focusing on the assembly, disassembly, maintenance and function of this macromolecular structure. 相似文献
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As part of a long-term study of the substitution reactions of piano-stool type cyclopentadienylmetal carbonyl complexes, several new methylcyclopentadienylmolybdenum compounds have been prepared and characterized by methods including IR spectroscopy, electrospray ionization mass spectrometry and X-ray crystallography. The complexes reported here include [{Cp′Mo(CO)3}2I]BPh4, cis-Cp′Mo(CO)2(PPh3)I and [Cp′Mo(CO)3(CH3CN)]BF4 (Cp′ = η5-C5H4CH3). In addition to their syntheses, comparisons are made between their IR spectroscopic and X-ray crystal structure data and those of similar complexes. 相似文献
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We develop a statistical thermodynamic model for the phase evolution of DNA-cationic lipid complexes in aqueous solution, as a function of the ratios of charged to neutral lipid and charged lipid to DNA. The complexes consist of parallel strands of DNA intercalated in the water layers of lamellar stacks of mixed lipid bilayers, as determined by recent synchrotron x-ray measurements. Elastic deformations of the DNA and the lipid bilayers are neglected, but DNA-induced spatial inhomogeneities in the bilayer charge densities are included. The relevant nonlinear Poisson-Boltzmann equation is solved numerically, including self-consistent treatment of the boundary conditions at the polarized membrane surfaces. For a wide range of lipid compositions, the phase evolution is characterized by three regions of lipid to DNA charge ratio, rho: 1) for low rho, the complexes coexist with excess DNA, and the DNA-DNA spacing in the complex, d, is constant; 2) for intermediate rho, including the isoelectric point rho = 1, all of the lipid and DNA in solution is incorporated into the complex, whose inter-DNA distance d increases linearly with rho; and 3) for high rho, the complexes coexist with excess liposomes (whose lipid composition is different from that in the complex), and their spacing d is nearly, but not completely, independent of rho. These results can be understood in terms of a simple charging model that reflects the competition between counterion entropy and inter-DNA (rho < 1) and interbilayer (rho > 1) repulsions. Finally, our approach and conclusions are compared with theoretical work by others, and with relevant experiments. 相似文献
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hnRNP complexes: composition, structure, and function. 总被引:28,自引:0,他引:28
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Audra F. Lugo 《Inorganica chimica acta》2010,363(10):2104-2511
A series of metal complexes have been prepared using two similar ketiminato ligands, ArL1H (([RN(H)(C(Me))2C(Me)O], ((R = 2,6-diisopropylphenyl (Dipp) or 2,6-dimethylphenyl, (Dmp)) and the less bulky, multidentate molecule L2H, ([RN(H)C(Me)CHC(Me)O] (R = C2H4NEt2)). Reaction of ArL1H or ArL1Na with Co(SCN)2, Eu(OTf)3 and Cu(OTf)2, afforded [Co(DippL1H)2(NCS)2] (1), [Eu(DippL1H)3(OTf)3] (2), and [Cu(OTf)2(DippL1H)2] (3). The coordination preferences of ArL1 and L2 with FeBr2 were investigated and yielded crystals of [Fe(DippL1)2] (4), [L2FeBr·LiBr(THF)2] (5), and [{(DmpNC(Me))2C(H)Me}FeBr2] (6). Complexes 1-6 have been structurally characterized by X-ray crystallography, and other pertinent techniques. 相似文献
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Mechanical and physiological processes contribute to joint tissue adaptations during growth and exercise and after injury. Those adaptations are often in response to the mechanotransductive stimuli linked to the transmission of forces across these load-bearing structures. Muscle-tendon interactions have been explored during skeletal loading and describe the relation of sarcomere shortening at the expense of tendon lengthening(1,2). The effects of load transmission through the bone-tendon and bone-ligament complexes, however, have not been studied as extensively, although both disuse and exercise will alter the stiffness of these significant structures. Recently, however, renewed interest has emerged about the pathogenesis underlying enthesopathies and enthesitis, and investigators are beginning to reveal the intricacies of bone-tendon and bone-ligament complexes(3,4,5). Here, we summarize the structure and function of the types of entheses between bone-tendon and bone-ligament, and relate how mechanical loading leads to functional adaptation, and at times, entheseal pathophysiology. 相似文献
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The bis(cyclopentadienyl) complexes [Cp2Ti(dca)]2O and Cp2V(dca)2 (dca = dicyanamide) have been prepared by reaction of sodium dicyanamide with aqueous solution of titanocene dichloride and vanadocene dichloride, respectively. The X-ray structure analyses of both complexes confirmed monodentate coordination of dicyanamide ligand through the terminal nitrogen atom of cyano group. 相似文献
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U P Singh B N Singh A K Ghose R K Singh A Sodhi 《Journal of inorganic biochemistry》1991,44(4):277-282
Complexes of 5-iodouracil (5IU) with Mn(II), Co(II), Cu(II), Zn(II), and Cd(II) ions have been prepared, characterized, and subjected to a screening system for evaluation of antitumor activity against Sarcoma-180 (S-180) and L 929 tumor cells. The complexes were characterized by their elemental analysis, infrared spectra, electronic spectra, magnetic measurements, and powder x-ray diffraction. The antitumor activity results indicate that some complexes have good antitumor activity both in vivo and in vitro against S-180 and L 929 tumor cells. 相似文献
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Twenty-eight rhodium, iridium or ruthenium complexes were evaluated for their in vitro antifungal activities against Candida albicans and Candida tropicalis. Fourteen compounds showed an antifungal activity against C. albicans and C. tropicalis with a range of the minimum inhibitor concentrations (MICs) between 16 and 250 micrograms/mL. 相似文献