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Formed Complexes (formed + complex)
Selected AbstractsTreatment with rapamycin prevents fibrosis in tight-skin and bleomycin-induced mouse models of systemic sclerosisARTHRITIS & RHEUMATISM, Issue 8 2010Ayumi Yoshizaki Objective Rapamycin, a novel macrolide immunosuppressive drug, is increasingly used as an agent for posttransplant immunosuppression and treatment of autoimmune disease. The molecular mechanism related to rapamycin-mediated immunosuppression is that rapamycin binds to FK-506 binding protein 12, and the formed complex inhibits the function of the mammalian target of rapamycin (mTOR), which in turn reduces protein phosphorylation, cell cycle progression, and cytokine production. The aim of this study was to examine the effect of rapamycin against the development of fibrosis and autoimmunity in 2 different types of systemic sclerosis (SSc) model mice. Methods Tight skin (TSK/+) mice and bleomycin- induced SSc model mice were used to evaluate the effect of rapamycin on fibrosis and immunologic abnormalities. Furthermore, the antifibrotic effect of rapamycin was assessed using TSK/+ mouse fibroblasts. Results Treatment with rapamycin reduced skin fibrosis of TSK/+ mice and skin and lung fibrosis of bleomycin-induced SSc model mice. The production of fibrogenic cytokines, such as interleukin-4 (IL-4), IL-6, IL-17, and transforming growth factor ,1, was attenuated by rapamycin. Hypergammaglobulinemia and anti,topoisomerase I antibody production were also reduced by rapamycin treatment in TSK/+ mice. In addition, mTOR expression levels were increased in TSK/+ mouse fibroblasts compared with those in wild-type mouse fibroblasts. Rapamycin treatment inhibited proliferation and collagen production of TSK/+ mouse fibroblasts in a dose-dependent manner. Conclusion This study is the first to show that rapamycin has a significant inhibitory effect on fibrosis in both TSK/+ and bleomycin-induced SSc model mice. These results suggest that rapamycin might be an attractive candidate for clinical trials in SSc patients. [source] Circular dichroism spectroscopic study of non-covalent interactions of poly- L -glutamic acid with a porphyrin derivative in aqueous solutionsJOURNAL OF PEPTIDE SCIENCE, Issue 9 2005Palivec Abstract The interactions of poly- L -glutamic acid and a cationic porphyrin derivative in aqueous solutions were studied by the combination of vibrational circular dichroism (VCD) and electronic circular dichroism (ECD) spectroscopies. It was found that non-covalent interactions between both agents influence the structure of the polymeric matrix and the guest porphyrins and vice versa, but the physico-chemical properties of the solutions, especially the pH and the relative permittivity of the solvent, play a key role in the structure of the polypeptide part of the formed complexes. It was shown that the interaction with porphyrins prevents the precipitation of poly- L -glutamic acid in aqueous solution at acidic pH. In special conditions, the porphyrins attached to the polypeptide probably possess face-to-face interaction as demonstrated by the enhancement of the characteristic ECD signal and the appearance of sidebands on its short and long wavelength sides. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd. [source] Iron halide mediated atom transfer radical polymerization of methyl methacrylate with N -alkyl-2-pyridylmethanimine as the ligandJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 19 2004Huiqi Zhang Abstract The controlled atom transfer radical polymerization (ATRP) of methyl methacrylate (MMA) catalyzed by iron halide/N -(n -hexyl)-2-pyridylmethanimine (NHPMI) is described. The ethyl 2-bromoisobutyrate (EBIB)-initiated ATRP with [MMA]0/[EBIB]0/[iron halide]0/[NHPMI]0 = 150/1/1/2 was better controlled in 2-butanone than in p -xylene at 90 °C. Initially added iron(III) halide improved the controllability of the reactions in terms of molecular weight control. The p -toluenesulfonyl chloride (TsC1)-initiated ATRP were uncontrolled with [MMA]0/[TsC1]0/[iron halide]0/[NHPMI]0 = 150/1/1/2 in 2-butanone at 90 °C. In contrast to the EBIB-initiated system, the initially added iron(III) halide greatly decreased the controllability of the TsC1-initiated ATRP. The ration of iron halide to NHPMI significantly influenced the controllability of both EBIB and TsC1-initiated ATRP systems. The ATRP with [MMA]0/[initiator]0/[iron halide]0/[NHPMI]0 = 150/1//1/2 provided polymers with PDIs , 1.57, whereas those with [iron halide]0/[NHPMI]0 = 1 resulted in polymers with PDIs as low as 1.35. Moreover, polymers with PDIs of approximately 1.25 were obtained after their precipitation from acidified methanol. The high functionality of the halide end group in the obtained polymer was confirmed by both 1H NMR and a chain-extenstion reaction. Cyclic voltammetry was utilized to explain the differing catalytic behaviors of the in situ -formed complexes by iron halide and NHPMI with different molar ratios. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4882,4894, 2004 [source] Structural compatibility of novel nucleotide modifications with shortened linkages designed for antigene/antisense therapyJOURNAL OF RAMAN SPECTROSCOPY, Issue 5 2004J. Hanu Abstract The impact of isopolar shortened internucleotide linkage modification on the hybridization properties of potential antisense or antigene oligonucleotides was studied by using a model molecular system consisting of polyuridylic acid (PolyU) and analogs of diadenosine monophosphate with the modified linkage. Raman spectra of mixed aqueous solutions were measured at various temperatures and compositions of the mixtures for four types of modified linkage and natural ApA (3,,5,) as a reference. Analysis of the spectral sets provided amounts of formed complexes and their Raman spectra. It has been found that as in the case of ApA (3,,5,), the studied ApA analogs form with PolyU triplex-like complexes containing a central pseudo-chain of closely arranged adenosine dimers. In the case of S - and R -configured 2,,5, and 3,,5, ApCOH A analogs, respectively, the amounts of complexes formed even exceed the ApA. This hybridization effectiveness is reached, however, by a more feasible prolongation of the pseudo-chain, while the stability constant for the initiation step is significantly lower. Raman spectra of the complexes showed that for both of the above analogs the structural compatibility with the natural nucleic acid chain is decreased, because of the distorted position of one adenine residue. This distortion influences the Watson,Crick hydrogen bonds. The two types of linkages may be suitable just for construction of longer antigene or antisense oligonucleotides with alternating lengthened and shortened linkages. There is, however, a warning of possible decreased binding specificity. Copyright © 2004 John Wiley & Sons, Ltd. [source] | ||||||||||