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排序方式: 共有318条查询结果,搜索用时 31 毫秒
31.
Terauchi T Asai N Doko T Taguchi R Takenaka O Sakurai H Yonaga M Kimura T Kajiwara A Niidome T Kume T Akaike A Sugimoto H 《Bioorganic & medicinal chemistry》2007,15(22):7098-7107
We present efficient syntheses of serofendic acids A and B (SA-A and SA-B), novel neuroprotective substances isolated from fetal calf serum. Biological and pharmacological evaluation showed that SA-A and SA-B have potent protective action against glutamate-induced neurotoxicity, but do not interact directly with glutamate receptors. A pharmacokinetic study showed that they have good oral bioavailability in rats. The results indicate that SA-A and SA-B are potential lead compounds for candidate drugs to treat various neurological disorders. 相似文献
32.
33.
Castillon GA Aguilera-Romero A Manzano-Lopez J Epstein S Kajiwara K Funato K Watanabe R Riezman H Muñiz M 《Molecular biology of the cell》2011,22(16):2924-2936
Glycosylphosphatidylinositol (GPI)-anchored proteins are secretory proteins that are attached to the cell surface of eukaryotic cells by a glycolipid moiety. Once GPI anchoring has occurred in the lumen of the endoplasmic reticulum (ER), the structure of the lipid part on the GPI anchor undergoes a remodeling process prior to ER exit. In this study, we provide evidence suggesting that the yeast p24 complex, through binding specifically to GPI-anchored proteins in an anchor-dependent manner, plays a dual role in their selective trafficking. First, the p24 complex promotes efficient ER exit of remodeled GPI-anchored proteins after concentration by connecting them with the COPII coat and thus facilitates their incorporation into vesicles. Second, it retrieves escaped, unremodeled GPI-anchored proteins from the Golgi to the ER in COPI vesicles. Therefore the p24 complex, by sensing the status of the GPI anchor, regulates GPI-anchored protein intracellular transport and coordinates this with correct anchor remodeling. 相似文献
34.
We examined the expression of recombination-activating genes (RAG-1 and RAG-2) and activation-induced cytidine deaminase (AID) by mature human blood B cells stimulated with anti-CD40 in the presence of IL-4 or IL-13. IL-4 was an effective cofactor for RAG-1 and RAG-2 expression, whereas IL-13 was not. In addition, IL-4-dependent RAG expression combined with AID and IgE expression allowed predominant expression of newly rearranged lambda light chains on IgE+ cells generated from kappa+ cells. Although the magnitudes of IL-4- and IL-13-dependent AID and IgE expression were related to expression levels of binding subunits of the IL-4 and IL-13 receptors, IL-13 was ineffective for light chain replacement in the induced IgE+ cells due to the failure in RAG expression. Our studies using mature blood B cells indicate that IL-4-responsive cells, unlike IL-13-responsive cells, undergo lambda gene rearrangement leading to replacement in parallel with RAG expression and suggest that this replacement may contribute to the regulation of affinity maturation of IgE antibodies. 相似文献
35.
Shimura K Nameki D Kajiwara K Watanabe K Sakagami Y Oishi S Fujii N Matsuoka M Sarafianos SG Kodama EN 《The Journal of biological chemistry》2010,285(50):39471-39480
Human immunodeficiency virus (HIV) gp41 plays a key role in viral fusion; the N- and C-terminal heptad repeats (N-HR and C-HR) of gp41 form a stable 6-helical conformation for fusion. Therefore, HR-derived peptides, such as enfuvirtide (T-20), inhibit HIV-1 fusion by acting as decoys, and have been used for the treatment of HIV-1 infection. However, the efficacy of T-20 is attenuated by resistance mutations in gp41, including V38A and N43D. To suppress the resistant variants, we previously developed electrostatically constrained peptides, SC34 and SC34EK, and showed that both exhibited potent anti-HIV-1 activity against wild-type and T-20-resistant variants. In this study, to clarify the resistance mechanism to this next generation of fusion inhibitors, we selected variants with resistance to SC34 and SC34EK in vitro. The resistant variants had multiple mutations in gp41. All of these mutations individually caused less than 6-fold resistance to SC34 and SC34EK, indicating that there is a significant genetic barrier for high-level resistance. Cross-resistance to SC34 and SC34EK was reduced by a simple difference in the polarity of two intramolecular electrostatic pairs. Furthermore, the selected mutations enhanced the physicochemical interactions with N-HR variants and restored activities of the parental peptide, C34, even to resistant variants. These results demonstrate that our approach of designing gp41-binding inhibitors using electrostatic constraints and information derived from resistance studies produces inhibitors with enhanced activity, high genetic barrier, and distinct resistance profile from T-20 and other inhibitors. Hence, this is a promising approach for the design of future generation peptide fusion inhibitors. 相似文献
36.
We have previously reported the efficient conversion of lactose into 3′-sialyllactose by high cell density cultures of a genetically engineered Escherichia coli strain expressing the Neisseria meningitidis gene for α-(2→3)-sialyltransferase [Fierfort, N.; Samain, E. J. Biotechnol. 2008, 134, 261-265.]. First attempts to use a similar strategy to produce 6′-sialyllactose with a strain expressing α-(2→6)-sialyltransferase from the Photobacterium sp. JT-ISH-224 led to the production of a trisaccharide that was identified as KDO-lactose (2-keto-3-deoxy-manno-octonyllactose). This result showed that α-(2→6)-sialyltransferase was able to use CMP-KDO as sugar donor and preferentially used CMP-KDO over CMP-Neu5Ac. By reducing the expression level of the sialyltransferase gene and increasing that of the neuABC genes, we have been able to favour the formation of 6′-sialyllactose and to prevent the formation of KDO-lactose. However, in this case, a third lactose derivative, which was identified as 6,6′-disialyllactose, was also produced. Formation of 6,6′-disialyllactose was mainly observed under conditions of lactose shortage. On the other hand, when the culture was continuously fed with an excess of lactose, 6′-sialyllactose was almost the only product detected and its final concentration was higher than 30 g/L of culture medium. 相似文献
37.
Saita Y Kodama E Orita M Kondo M Miyazaki T Sudo K Kajiwara K Matsuoka M Shimizu Y 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(5):3116-3122
The chemokine receptor CCR5 is an attractive target for HIV-1 drug development, as individuals whose cells lack surface CCR5 expression are highly resistant to HIV-1 infection. CCR5 ligands, such as CCL5/RANTES, effectively inhibit HIV-1 infection by competing for binding opportunities to the CCR5 and inducing its internalization. However, the inherent proinflammatory activity of the chemotactic response of CCR5 ligands has limited their clinical use. In this study, we found that a novel small molecule, functionally selective CCR5 agonist, 2,2-dichloro-1-(triphenylphosphonio)vinyl formamide perchlorate (YM-370749), down-modulates CCR5 from the cell surface without inducing a chemotactic response and inhibits HIV-1 replication. In molecular docking studies of YM-370749 and a three-dimensional model of CCR5 based on the rhodopsin crystal structure as well as binding and functional studies using various CCR5 mutants, the amino acid residues necessary for interaction with YM-370749 were marked. These results provide a structural basis for understanding the activation mechanism of CCR5 and for designing functionally selective agonists as a novel class of anti-HIV-1 agents. 相似文献
38.
Kagesawa T Nakamura Y Nishikawa M Akiyama Y Kajiwara M Matsuno K 《Mechanisms of development》2008,125(11-12):1020-1032
Homoplasy is a phenomenon in which organisms in different phylogenetic groups independently acquire similar traits. However, it is largely unknown how developmental mechanisms are altered to give rise to homoplasy. In the genus Drosophila, all species of the subgenus Sophophora, including Drosophila (D.) melanogaster, have eggshells with two dorsal appendages (DAs); most species in the subgenus Drosophila, including D. virilis, and in the subgenus Dorsilopha, have four-DAs. D. melanica belongs to the Drosophila subgenus, but has two-DAs, and phylogenetic analyses suggest that it acquired this characteristic independently. The patterning of the DAs is tightly regulated by epidermal growth factor receptor (EGFR) signaling in D. melanogaster. Previous studies suggested that a change in the EGFR signal activation pattern could have led to the divergence in DA number between D. melanogaster and D. virilis. Here, we compared the patterns of EGFR signal activation across the Drosophila subgenera by immunostaining for anti-activated MAP kinase (MAPK). Our analysis revealed distinct patterns of EGFR signal activation in each subgenus that was consistent with their phylogenetic relationship. In addition, the number of DAs always corresponded to the number of EGFR signaling activation domains in two, three, and four-DA species. Despite their common two-DA characteristic, the EGFR signaling activation pattern in D. melanica diverged significantly from that of species in the subgenus Sophophora. Our results suggest that acquisition of the homoplastic two-DA characteristic could be explained by modifications of the EGFR signaling system in the genus Drosophila that occurred independently and at least twice during evolution. 相似文献
39.
Y Hiragi H Inoue Y Sano K Kajiwara T Ueki H Nakatani 《Journal of molecular biology》1990,213(3):495-502
The self-assembly process of tobacco mosaic virus protein (TMVP) was observed by rapid temperature-jump time-resolved solution X-ray small-angle scattering using synchrotron radiation. The temperature-jump device used for the X-ray measurements is rapid enough to cope with even the fastest-assembling process of TMVP, and accumulates data of reasonable signal-to-noise ratios with a minimum total counting time of 7.5 seconds. The measurements suggested that the 20 S disk of TMVP polymerized to stacked disks (short rods). The time to complete stacking varied from approximately 25 seconds to approximately 1200 seconds, depending on the solution condition and magnitude of the temperature gap. Higher protein concentration, ionic strength and temperature favoured faster association. The results were analysed in terms of a set of kinetic equations that describe the two-stage aggregation of TMVP with an equilibrium constant K1, and two rate constants k+2 and k-2 for association and dissociation of disks, respectively. The consistency of the analysis suggests that the TMVP assembly proceeds in two steps of: (1) the aggregation of A-proteins into double-layered disks; and (2) the stacking of double-layered disks. The kinetic analysis indicated that the stacking belongs to the lowest range of protein-protein interaction system. 相似文献
40.