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991.
TAK-599, a novel N-phosphono type prodrug of anti-MRSA cephalosporin T-91825: synthesis,physicochemical and pharmacological properties 总被引:3,自引:0,他引:3
Ishikawa T Matsunaga N Tawada H Kuroda N Nakayama Y Ishibashi Y Tomimoto M Ikeda Y Tagawa Y Iizawa Y Okonogi K Hashiguchi S Miyake A 《Bioorganic & medicinal chemistry》2003,11(11):2427-2437
Crystalline 1 (TAK-599) is a novel N-phosphono prodrug of anti-methicillin-resistant Staphylococcus aureus (MRSA) cephalosporin 2a (T-91825) that has high affinity for penicillin-binding protein (PBP) 2' (IC(50); 0.90 microg/mL) and shows potent in vitro anti-MRSA activity (MIC against MRSA N133; 1.56 microg/mL), comparable to that of vancomycin (1.56 microg/mL). Although 2a had insufficient water solubility (2.3 mg/mL) for parenteral administration, 1 showed excellent water solubility (>100 mg/mL, pH 7) as well as good chemical stability in the solid state and solution. In pharmacokinetic studies, when 1 was administered intravenously to rats and monkeys, it was rapidly converted into 2a in the blood. These results show that 1 (TAK-599) is a highly promising parenteral cephalosporin targeted for MRSA infection. 相似文献
992.
A photoinduced hydrogen production system that couples sucrose degradation with invertase and glucose dehydrogenase (GDH) and hydrogen production with colloidal platinum as a catalyst using visible light-induced photosensitization of artificial Zn chlorophyll-a (Zn Chl-a) has been developed. Continuous hydrogen gas production over more than 240 min was observed when the reaction mixture containing sucrose, invertase, GDH, nicotinamide adenine dinucreotide (NAD(+)), Zn Chl-a, methyl viologen (MV(2+), an electron relay reagent), and colloidal platinum was irradiated by visible light. Zn Chl-a was superior to that of Mg Chl-a in photostability and photosensitization activity. 相似文献
993.
Li A Kato Z Ohnishi H Hashimoto K Matsukuma E Omoya K Yamamoto Y Kondo N 《Protein expression and purification》2003,32(1):110-118
Human interleukin-18 (hIL-18), originally known as an IFN-gamma-inducing factor, is a recently cloned cytokine that is secreted by Kupffer cells of the liver and by stimulated macrophages. We have previously established a method of expression and purification of IL-18. The yield however remains low and the insufficient expression of a heterologous protein could be due to skewed codon usage between the expression host and the cDNA donor. The sequence of mature hIL-18 has 37 a.a. rare codons for Escherichia coli in a total of 157 a.a. To overcome this problem, gene synthesis was performed with optimized codons for the expression host E. coli. The final yield of the hIL-18 protein with optimized codons was about five times higher than the yield with the native sequence. Using a minimal medium, this system produces large quantities of labeled proteins that can be used in NMR analysis. Our simple and efficient production system can be applied to the production of other cytokines for new structural and therapeutic use. 相似文献
994.
Phenylketonuria (PKU) is a metabolic disorder that results from a deficiency of hepatic phenylalanine hydroxylase (PAH). Identification
of the PKU genotype is useful for predicting clinical PKU phenotype. More than 400 mutations resulting in PAH deficiency have
been reported worldwide. We used a genedetecting instrument to identify the nine prevalent Japanese mutations in the PAH gene
among 31 PKU patients as a preliminary study. This instrument can automatically detect mutations through the use of allele-specific
oligonucleotide (ASO) capture probes, and gave results comparable to those of sequencing studies. Each country has uniquely
prevalent and specific mutations causing PKU, and less than 50 types of such mutations are generally present in each country.
Early genotyping of PKU makes it possible to identify the phenotype and select the optimal therapy for the disease. For early
genotyping, the instrumental method described here shortens the time required for genotyping based on mRNA and/or genomic
DNA of PKU parents. 相似文献
995.
To facilitate swift structural characterizations, structural genomic/proteomic projects need to divide large multi-domain proteins into structural domains and to determine their structures separately. Thus, the assignment of structural domains based solely on sequence information, especially on the physico-chemical properties of the amino acid sequences, could be very helpful for such projects. In this study, we examined the characteristics of domain linker sequences, which are loop sequences connecting two structural domains. To this end, we prepared a set of 101 non-redundant multi-domain protein sequences with known structures, and performed an analysis of the linker sequences. The analysis revealed that the frequencies of five (Pro, Gly, Asp, Asn, Lys) amino acid residues differed significantly between the linker and non-linker loop sequences. Moreover, we observed a similar deviation for the residue pair frequencies between the two types of loop sequences. Finally, we describe an automated method, based on the above analysis, to detect loops that have high probabilities of being domain linkers in a protein sequence. 相似文献
996.
Adachi K Izumi M Osano Y Miura N Takatsu S Terao S Mitsuma T 《Experimental biology and medicine (Maywood, N.J.)》2003,228(9):1069-1071
To study the pathophysiology of the neuronal degeneration in vitamin B12 deficiency, we investigated the concentrations of the polyamines putrescine, spermidine, and spermine in brain regions and liver using high-performance liquid chromatography with fluorescence detection. Male Wistar rats were fed either a control or vitamin B12-deficient diet for 20 weeks. No remarkable behavioral changes were observed. Serum vitamin B12 and hepatic methionine concentrations were significantly lower and hepatic homocysteine was elevated in rats fed vitamin B12-deficient diet than in controls. Vitamin B12 deficiency was associated with decreased concentrations of spermidine, spermidine in liver and some regions of brain, although there were no observed abnormalities in behavior. These results suggest that vitamin B12 deficiency may play a role in neuronal degeneration through the disturbance of polyamine concentrations in rat brain. 相似文献
997.
Retinoic acid isomers produce malformations in postembryonic development of the Japanese flounder,Paralichthys olivaceus 总被引:3,自引:0,他引:3
We previously reported that characteristic deformities were induced by retinoic acid (RA) treatment of the Japanese flounder, Paralichthys olivaceus, at 6-9 days post-hatching (dph). To evaluate the toxic potency of nuclear retinoid receptors in induction of deformities by RA, we here investigated the effects of retinoic acid isomers on postembryonic development of this species. Larvae were exposed to either 25 nM of all-trans RA (atRA), 9-cis RA (9cRA) or 13-cis RA (13cRA) at 6-9 dph. All RA isomers induced deformities in the lower jaw, caudal fin and vertebrae. In the lower jaw, growth retardation of the dentary was evident. In the vertebrae, the major abnormalities were hypertrophy of the centrum, central fusion, and an increase in the number of abdominal vertebrae. Caudal fin deformities included deformity of caudal bone complex and absence of the entire caudal fin. The absence of the hypural primordium at 12 dph was the first sign of abnormality in caudal fin development, and resulted in complete blocking of the caudal fin development. Among the RA isomers, atRA induced the most severe deformity in all skeletons examined. Retinoic acid receptor (RAR) expression was activated by atRA and 9cRA, and pitx2 expression was inhibited in the lower jaw by atRA and 9cRA. Vitamin D receptor (VDR) expression was specifically inhibited by atRA treatment, suggesting that RA inhibits the lower jaw growth by suppressing the expression of these genes. These results suggest that RA exerted toxic effects on the skeletal systems, mainly through the RAR pathway. 相似文献
998.
Spiking characteristics of neurons in the middle temporal (MT) area and the medial superior temporal (MST) area in the visual cortex of a monkey are compared with the ones in the principal sulcus (PS) area in the prefrontal cortex. The comparison is based on the basis of three inter-spike interval statistical measures: the coefficient of variation (CV), the skewness coefficient (SK) and the correlation coefficient of consecutive intervals (COR). Even for the spike sequences recorded from the same neuron, three coefficients computed from 100 intervals do not always exhibit similar values, but distribute rather widely. The distribution of three coefficients obtained from a single neuron in the MST area does not largely deviate from the distribution obtained from multiple neurons in MT and MST areas. Those distributions, however, largely deviate from the distribution obtained from neurons in the PS area. In this way, the distribution of those statistical coefficients reflects the nature of the recording site. 相似文献
999.
Isolation,characterization, and cDNA sequence of a carotenoid binding protein from the silk gland of Bombyx mori larvae 总被引:6,自引:0,他引:6
Tabunoki H Sugiyama H Tanaka Y Fujii H Banno Y Jouni ZE Kobayashi M Sato R Maekawa H Tsuchida K 《The Journal of biological chemistry》2002,277(35):32133-32140
A carotenoid binding protein (CBP) has been isolated from the silk glands of Bombyx mori larvae. The protein has an apparent molecular mass of 33 kDa and binds carotenoids in a 1:1 molar ratio. Lutein accounts for 90% of the bound carotenoids, whereas alpha-carotene and beta-carotene are minor components. Immunological analysis demonstrated the presence of CBP only in the yellow-colored tissues of the silk gland, midgut, testis, and ovary. Several phenotypes of B. mori mutants linked to carotenoid transport have been utilized to characterize CBP. The Y (yellow hemolymph) gene controls uptake of carotenoids from the midgut lumen into the midgut epithelium, and larvae with the +(Y) gene lack this property. Immunoblotting analysis confirmed the presence of CBP in mutants with the dominant Y gene only. Immunohistochemistry verified the localization of CBP in the villi of the midgut epithelium, indicating that CBP might be involved in absorption of carotenoids. A cDNA clone for CBP encoding a protein of 297 amino acids has been isolated from the B. mori silk gland cDNA library. The deduced amino acid sequence revealed that CBP is a novel member of the steroidogenic acute regulatory (StAR) protein family with its unique structural feature of a StAR-related lipid transfer domain, known to aid in lipid transfer and recognition. Lutein-binding capacity of the recombinant CBP (rCBP) determined by incubating rCBP with lutein followed by immunoprecipitation using anti-CBP IgG conjugated to protein A-Sepharose, demonstrated the formation of a lutein-rCBP complex. Sequence analyses coupled with binding specificity suggest that CBP is a new member of the StAR protein family that binds carotenoids rather than cholesterol. 相似文献
1000.
Isolation of cathepsin B inhibitory peptides,Cabin-A1 and -A2, from a tryptic and chymotryptic hydrolysate of human serum albumin 总被引:2,自引:0,他引:2
Nakagomi K Takatsu K Takagi S Ebisu H Sadakane Y Fujii N Akizawa T Tanimura T Hatanaka Y 《Peptides》2002,23(9):1567-1571
Two novel peptides that inhibit cathepsin B were isolated from a tryptic and chymotryptic hydrolysate of human serum albumin, and designated as Cabin-A1 and -A2. Cabin-A1 and -A2 were purified by reversed-phase HPLC and identified as Ser-Leu-His-Thr-Leu-Phe and Phe-Gln-Asn-Ala-Leu, respectively. These peptides correspond to f(65-70) and f(403-407) of human serum albumin. Human albutensin A (Ala-Phe-Lys-Ala-Trp-Ala-Val-Ala-Arg), which corresponds to f(210-218), was also isolated as a potent cathepsin B inhibitor. Synthetic Cabin-A1, -A2, and human albutensin A showed dose-dependent inhibition of cathepsin B, with K(i) values of 2.4, 290, and 3.8 microM, respectively. 相似文献