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101.
Nishizawa R Nishiyama T Hisaichi K Matsunaga N Minamoto C Habashita H Takaoka Y Toda M Shibayama S Tada H Sagawa K Fukushima D Maeda K Mitsuya H 《Bioorganic & medicinal chemistry letters》2007,17(3):727-731
Hydroxylated derivatives were designed and synthesized based on the information of oxidative metabolites. Compounds derived from beta-substituted (2R,3R)-2-amino-3-hydroxypropionic acid showed improved inhibitory activities against the binding of MIP-1alpha to human CCR5, compared with the non-hydroxylated derivatives and the other isomers. 相似文献
102.
Teno N Miyake T Ehara T Irie O Sakaki J Ohmori O Gunji H Matsuura N Masuya K Hitomi Y Nonomura K Horiuchi M Gohda K Iwasaki A Umemura I Tada S Kometani M Iwasaki G Cowan-Jacob SW Missbach M Lattmann R Betschart C 《Bioorganic & medicinal chemistry letters》2007,17(22):6096-6100
Pyrrolopyrimidine, a novel scaffold, allows to adjust interactions within the S3 subsite of cathepsin K. The core intermediate 10 facilitated the P3 optimization and identified highly potent and selective cathepsin K inhibitors 11-20. 相似文献
103.
104.
Rad50 is involved in MMS-induced recombination between homologous chromosomes in mitotic cells 总被引:2,自引:0,他引:2
Tomizawa Y Ui A Onoda F Ogiwara H Tada S Enomoto T Seki M 《Genes & genetic systems》2007,82(2):157-160
The structural maintenance of chromosomes (SMC) family proteins (Smc1-Smc6) typically consist of two coiled-coil domains, an amino-terminal head domain, and a carboxyl-terminal tail domain. Rad50, a component of the Mre11/Rad50/Xrs2 (MRX) complex, has a similar domain structure to the SMC proteins. In Saccharomyces cerevisiae, the MRX complex appears to be essential for recombination between homologous chromosomes in meiotic cells, but not in cells undergoing vegetative growth. Here we provide for the first time evidence that Rad50, like Smc6, is required for the induction of recombination between homologous chromosomes in cells in the vegetative growth state upon exposure to methyl methanesulfonate. However, UV-induced recombination between homologous chromosomes is intact in both rad50 and smc6-56 mutant cells. 相似文献
105.
Senpuku H Tada A Nakao R Yonezawa H Yoneda S Yoshihara A Miyazaki H 《FEMS immunology and medical microbiology》2007,49(1):84-90
The amino acid residues 361-386 of Streptococcus mutans PAc includes an important region associated with the interaction between S. mutans and salivary components. We investigated the relationships between levels of the anti-PAc (361-386) peptide antibody (PPA) in saliva and periodontal status in 281 elderly subjects (mean age 77 years; 118 females, 163 males) by assessing dental calculus (CA), attachment loss (AL), pocket depth (PD), bleeding on probing (BOP) and various blood parameters. Enzyme-linked immunosorbent assay results revealed that subjects with a PPA level of greater than 0.1 (PPA detected group) showed a lower average value for number of sites with more than 6 mm of AL/6 points x 100/tooth (rAL6) than those with a PPA level of less than 0.1 (PPA not detected group). Furthermore, average values for rAL6 were significantly lower in the PPA detected group, and BOP, AL and rAL6 correlated positively and significantly with the percentage of eosinophils present in leukocytes in female subjects in both groups. PPA level had a negative correlation with percentages of basophils and eosinophils. The results indicate that systemic increases in numbers of eosinophils and basophils are associated with the development of periodontal diseases, while PPA level may be a useful indicator of periodontal status. 相似文献
106.
Role of the Cytosolic Heat Shock Protein 70 Ssa5 in the Ciliate Protozoan Tetrahymena thermophila 下载免费PDF全文
Yasuhiro Fukuda Takahiko Akematsu Rizwan Attiq Chika Tada Yutaka Nakai Ronald E. Pearlman 《The Journal of eukaryotic microbiology》2015,62(4):481-493
Heat shock protein 70 (Hsp70) is a member of a family of conserved chaperone proteins whose function is well investigated in many model organisms. Here we focus on an Hsp70 called Ssa5 in the ciliate protozoan Tetrahymena thermophila, and reveal that its translation is heat inducible as for general Hsps. Moreover, the protein is abundantly expressed in the cytoplasm during sexual reproduction (conjugation) as well as in response to heat‐stress. Knocking out of SSA5 (ΔSSA5) does not affect the survival of the cell under heat‐stress, likely due to other Hsp70 paralogs compensating for the defect. During conjugation, ΔSSA5 leads to a fertilization defect in which the two pronuclei are in close proximity but never fuse. The unfertilized pronuclei differentiate, resulting in a heterokaryon with developed haploid germline and somatic nuclei. In addition, degeneration of the parental somatic nucleus is not affected. These results suggest a specific involvement of Ssa5 in pronuclear fusion and fertilization. 相似文献
107.
Nishizawa R Nishiyama T Hisaichi K Minamoto C Murota M Takaoka Y Nakai H Tada H Sagawa K Shibayama S Fukushima D Maeda K Mitsuya H 《Bioorganic & medicinal chemistry》2011,19(13):4028-4042
Based on the original spirodiketopiperazine design framework, further optimization of an orally available CCR5 antagonist was undertaken. Structural hybridization of the hydroxylated analog 4 derived from one of the oxidative metabolites and the new orally available non-hydroxylated benzoic acid analog 5 resulted in another potent orally available CCR5 antagonist 6a as a clinical candidate. Full details of a structure-activity relationship (SAR) study and ADME properties are presented. 相似文献
108.
Yoshida M Mori A Morimoto S Kotani E Oka M Notoya K Makino H Ono M Shirasaki M Tada N Fujita H Ban J Ikeda Y Kawamoto T Goto M Kimura H Baba A Yasuma T 《Bioorganic & medicinal chemistry》2011,19(6):1881-1894
The calcium-sensing receptor antagonist (CaSR) has been recognized as a promising target of anabolic agents for treating osteoporosis. In the course of developing a new drug candidate for osteoporosis, we found tetrahydropyrazolopyrimidine derivative 1 to be an orally active CaSR antagonist that stimulated transient PTH secretion in rats. However, compound 1 showed poor physical and chemical stability. In order to work out this compound's chemical stability and further understand its in vivo efficacy, we focused on modifying the 2-position of the tetrahydropyrazolopyrimidine. As a result of chemical modification, we discovered (5R)-N-[1-ethyl-1-(4-ethylphenyl)propyl]-2,7,7-trimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide monotosylate 10m (TAK-075), which showed improved solubility, chemical stability, and in vivo efficacy. Furthermore, we describe that evaluating the active metabolite is important during repeated treatment with short-acting CaSR antagonists. 相似文献
109.
Tsumori Y Ndounga M Sunahara T Hayashida N Inoue M Nakazawa S Casimiro P Isozumi R Uemura H Tanabe K Kaneko O Culleton R 《PloS one》2011,6(8):e23430
The African continent is currently experiencing rapid population growth, with rising urbanization increasing the percentage of the population living in large towns and cities. We studied the impact of the degree of urbanization on the population genetics of Plasmodium falciparum in urban and peri-urban areas in and around the city of Brazzaville, Republic of Congo. This field setting, which incorporates local health centers situated in areas of varying urbanization, is of interest as it allows the characterization of malaria parasites from areas where the human, parasite, and mosquito populations are shared, but where differences in the degree of urbanization (leading to dramatic differences in transmission intensity) cause the pattern of malaria transmission to differ greatly. We have investigated how these differences in transmission intensity affect parasite genetic diversity, including the amount of genetic polymorphism in each area, the degree of linkage disequilibrium within the populations, and the prevalence and frequency of drug resistance markers. To determine parasite population structure, heterozygosity and linkage disequilibrium, we typed eight microsatellite markers and performed haplotype analysis of the msp1 gene by PCR. Mutations known to be associated with resistance to the antimalarial drugs chloroquine and pyrimethamine were determined by sequencing the relevant portions of the crt and dhfr genes, respectively. We found that parasite genetic diversity was comparable between the two sites, with high levels of polymorphism being maintained in both areas despite dramatic differences in transmission intensity. Crucially, we found that the frequencies of genetic markers of drug resistance against pyrimethamine and chloroquine differed significantly between the sites, indicative of differing selection pressures in the two areas. 相似文献
110.