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排序方式: 共有375条查询结果,搜索用时 125 毫秒
41.
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
42.
Akiba Y Suzuki R Saito-Saino S Owada Y Sakagami H Watanabe M Kondo H 《Gene expression patterns : GEP》2002,1(2):123-133
The gene expression for seven phosphatidylinositol phosphate kinases (PIPKs)-types Ialpha, Ibeta, Igamma, types IIalpha, IIbeta, IIgamma, and type III-was examined using in situ hybridization histochemistry, in the mouse brain during normal development. In the embryonic mouse brain, positive expression signals were detected only for the genes encoding PIPK Igamma and PIPK IIbeta in both the cerebral ventricular and mantle zones, with weaker signals in the former zone. On the other hand, the genes encoding all PIPKs were essentially detected in the external granule cell layer which represents the germinal zone for the neuronal granule cells. In the postnatal brain, among the seven PIPKs, the expression for genes encoding PIPK Igamma and IIbeta is evident in most gray matter, while the expression for the other five types was weak in the cortical gray matter and negligible in most non-cortical gray matter such as the diencephalon and brain stem nuclei. While the expression for most PIPKs in the mature hippocampus was distinct, the expression in the CA3 and the dentate gyrus was less definite for the genes encoding PIPK Ialpha and IIgamma, respectively. The distinct expression for the gene encoding PIPK IIalpha was detected in the postnatal white matter such as the cerebellar medulla, the corpus callosum, the hippocampal fimbriae, and the internal capsule. 相似文献
43.
Peptide signalling in plants 总被引:3,自引:0,他引:3
Peptide signals play crucial roles in all aspects of the plant life cycle. An understanding of peptide signal production and reception mechanisms is beginning to emerge. Studies on the signal-transduction cascades that follow the reception of peptide signals are just beginning. 相似文献
44.
Tsuji F Ishihara A Kurata K Nakagawa A Okada M Kitamura S Kanamaru K Masuda Y Murakami K Irie K Sakagami Y 《FEBS letters》2012,586(2):174-179
ComX pheromone is an isoprenoidal oligopeptide containing a modified tryptophan residue, which stimulates natural genetic competence in the gram-positive bacterium Bacillus. Since posttranslational prenylation on the tryptophan residue has not been reported except in ComX pheromone, the universality of this modification has not yet been elucidated. In this paper, we established a cell-free system, whereby the tryptophan residue in peptides is modified with a geranyl group by modifying enzyme ComQ. In addition, we investigated enzymatic reaction conditions using an in vitro enzyme reaction system. This is the first report of in vitro geranylation on the tryptophan residue. This system is potentially a useful tool for elucidating the universality of prenylation on the tryptophan residue. 相似文献
45.
Horváth G Molnár P Radó-Turcsi E Deli J Kawase M Satoh K Tanaka T Tani S Sakagami H Gyémánt N Molnár J 《Acta biochimica Polonica》2012,59(1):129-132
The aim of the present study was to compare carotenoid extracts of Rose hips (Rosa canina L.) with regard to their phytochemical profiles and their in vitro anti-Helicobacter pylori (H. pylori), cytotoxic, multidrug resistance (MDR) reversal and radical scavenging activity. Carotenoid composition was investigated in the different fractionation of rose hips, using extraction methods. Six main carotenoids - epimers of neochrome, lutein, zeaxanthin, rubixanthin, lycopene, β,β-carotene - were identified from Rose hips by their chromatographic behavior and UV-visible spectra, which is in accordance with other studies on carotenoids in this plant material. The active principles in the carotenoid extract might differ, depending upon the extraction procedures. 相似文献
46.
47.
Administration of 4-8 mg testosterone propionate significantly raised 25-hydroxycalciferol levels in the ultraviolet irradiated rats compared to the ultraviolet irradiated controls, but failed to influence serum 25-hydroxycalciferol levels in the non-irradiated animals. Estradiol benzoate and progesterone did not influence serum 25-hydroxycalciferol levels regardless of the ultraviolet irradiation. These findings implicate that testosterone enhances vitamin D biosynthesis induced by ultraviolet irradiation in rats, in accordance with the clinical observation that males often show higher levels of serum 25-hydroxycalciferol than females. 相似文献
48.
Norikazu Kawai Yukiteru Ouji Masaharu Sakagami Takashi Tojo Noriyoshi Sawabata Masahide Yoshikawa Shigeki Taniguchi 《Biochemistry and Biophysics Reports》2018
Decellularization of tissues is a recently developed technique mostly used to provide a 3-dimensional matrix structure of the original organ, including decellularized lung tissues for lung transplantation. Based on the results of the present study, we propose new utilization of decellularized tissues as inducers of stem cell differentiation. Decellularized lung matrix (L-Mat) samples were prepared from mouse lungs by SDS treatment, then the effects of L-Mat on differentiation of ES cells into lung cells were investigated. ES cell derived-embryoid bodies (EBs) were transplanted into L-Mat samples and cultured for 2 weeks. At the end of the culture, expressions of lung cell-related markers, such as TTF-1 and SP-C (alveolar type II cells), AQP5 (alveolar type I cells), and CC10 (club cells), were detected in EB outgrowths in L-Mat, while those were not found in EB outgrowths attached to the dish. Our results demonstrated that L-Mat has an ability to induce differentiation of ES cells into lung-like cells. 相似文献
49.
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