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101.
Yagi N Yano Y Hatanaka K Yokoyama Y Okuno H 《Bioorganic & medicinal chemistry letters》2007,17(9):2590-2593
A novel lipid analog based on amino acids for liposome modification was developed. It consisted of three different kinds of amino acid derivatives and two fatty acids, and can react directly with the peptide synthesized first on resin by Fmoc solid-phase synthesis. In this study, lipid analog conjugated with HIV-TAT peptide (domain of human immunodeficiency virus TAT protein) was synthesized and successfully incorporated into liposome. The liposome containing the lipopeptide bearing HIV-TAT exhibited efficient cellular uptake. 相似文献
102.
Ish T Sootome H King AJ Suda M Noro N Yamashita K Noumi T Ishii T 《Journal of biomolecular screening》2007,12(6):809-817
Checkpoint kinase 1 (Chk1), a serine/threonine kinase, plays an important role in DNA damage checkpoint control and is an attractive target for cancer treatment. To develop a Chk1-specific cell-based assay, stable clones were established in which Chk1 kinase domain fused at its N-terminus with p53 through 4 tandem repeats of Gly-Gly-Gly-Gly-Ser was expressed in an inducible manner. Chk1 kinase specificity of the phosphorylation of fused p53 was confirmed by the experiments with a kinase-inactive Chk1. Only in the presence of an inducer molecule was phosphorylation of p53 at Ser-15 in the stable clones induced. Furthermore, its assay performance proved acceptable for high-throughput screening applications, judging from the Z' factor values (> 0.77). Finally, the cell-based assay thus established yielded structure-activity relationship data for a small set of test inhibitors of Chk1 within cells. Collectively, these results demonstrate that the established cell-based assay provides a novel and highly sensitive cellular platform for Chk1 inhibitor discovery. 相似文献
103.
Endo N Kan-no N Nagahisa E 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2007,147(2):293-307
Alanopine dehydrogenase (AlDH) and three isoforms of strombine/alanopine dehydrogenase (St/AlDH) were purified from muscle tissue of the polychaete rockworm Marphysa sanguinea. The four enzymes, which can be distinguished by the isoelectric point, are monomeric 42 kDa proteins, possess similar pH-activity profiles, and display specificity for pyruvate and NAD(H). The three isoforms of St/AlDH show equivalent Km and Vmax for glycine and L-alanine and for D-strombine and meso-alanopine. Free amino acid levels in the muscle and D-strombine accumulation in vivo during muscle activity suggest that St/AlDHs function physiologically as StDH. AlDH shows specificity for L-alanine and meso-alanopine, but not for glycine or D-strombine. The amino acid sequences of AlDH and one of the St/AlDH isoforms were determined by a combination of amino acid sequence analysis and cDNA cloning. St/AlDH cDNA consisted of 1586 bp nucleotides that encode a 399-residue protein (43,346.70 Da), and AlDH cDNA consisted of 1587 bp nucleotides that encode a 399-residue protein (43,886.68 Da). The two amino acid sequences deduced from the cDNA displayed 67% amino acid identity, with greatest similarity to that of tauropine dehydrogenase from the polychaete Arabella iricolor. 相似文献
104.
Oba M Fukushima S Kanayama N Aoyagi K Nishiyama N Koyama H Kataoka K 《Bioconjugate chemistry》2007,18(5):1415-1423
A cyclic RGD peptide-conjugated block copolymer, cyclo[RGDfK(CX-)]-poly(ethylene glycol)-polylysine (c(RGDfK)-PEG-PLys), was synthesized from acetal-PEG-PLys under mild acidic conditions and spontaneously associated with plasmid DNA (pDNA) to form a polyplex micelle in aqueous solution. The cyclic RGD peptide recognizes alphavbeta3 and alphavbeta5 integrin receptors, which play a pivotal role in angiogenesis, vascular intima thickening, and the proliferation of malignant tumors. The c(RGDfK)-PEG-PLys/pDNA polyplex micelle showed a remarkably increased transfection efficiency (TE) compared to the PEG-PLys/pDNA polyplex micelle for the cultured HeLa cells possessing alphavbeta3 and alphavbeta5 integrins. On the other hand, in the transfection against the 293T cells possessing no alphavbeta3 and a few alphavbeta5 integrins, the TE of the c(RGDfK)-PEG-PLys/pDNA micelle showed no increase compared to the TE of the PEG-PLys/pDNA micelle. Flow cytometric analysis revealed a higher uptake of the c(RGDfK)-PEG-PLys/pDNA micelle than the PEG-PLys/pDNA micelle against HeLa cells, consistent with the transfection results. Furthermore, a confocal laser scanning microscopic observation revealed that the pDNA in the c(RGDfK)-PEG-PLys micelle preferentially accumulated in the perinuclear region of the HeLa cells within 3 h of incubation. No such fast and directed accumulation of pDNA to the perinuclear region was observed for the micelles without c(RGDfK) ligands. These results indicate that the increase in the TE induced by the introduction of the c(RGDfK) peptide ligand was due to an increase in cellular uptake as well as facilitated intracellular trafficking of micelles toward the perinuclear region via alphavbeta3 and alphavbeta5 integrin receptor-mediated endocytosis, suggesting that the cyclic RGD peptide-conjugated polyplex micelle has promising feasibility as a site-specifically targetable gene delivery system. 相似文献
105.
Yan H Saika H Maekawa M Takamure I Tsutsumi N Kyozuka J Nakazono M 《Genes & genetic systems》2007,82(4):361-366
Senescence or cell death in plant leaves is known to be inducible by darkness or H(2)O(2). When the Arabidopsis gene MAX2/ORE9 is disrupted, leaf senescence or cell death in response to the above stimuli is delayed. Because the rice (Oryza sativa L.) gene DWARF3 (D3) is orthologous to MAX2/ORE9, we wished to know whether disruption of D3 also results in increased longevity in leaves. We found that darkness-induced senescence or H(2)O(2)-induced cell death in the third leaf [as measured by chlorophyll degradation, membrane ion leakage and expression of senescence-associated genes (SAGs)] in a d3 rice mutant was delayed by 1-3 d compared to that in its reference line Shiokari. Moreover, the mRNA levels of D3, HTD1 and D10, which are orthologs of Arabidopsis MAX2/ORE9, MAX3 and MAX4, respectively, increased during cell death. These results suggest that D3 protein in rice, like MAX2/ORE9 in Arabidopsis, is involved in leaf senescence or cell death. 相似文献
106.
One of the simplest ways to predict ligand binding sites is to identify pocket-shaped regions on the protein surface. Many programs have already been proposed to identify these pocket regions. Examination of their algorithms revealed that a pocket intrinsically has two arbitrary properties, "size" and "depth". We proposed a new definition for pockets using two explicit adjustable parameters that correspond to these two arbitrary properties. A pocket region is defined as a space into which a small probe can enter, but a large probe cannot. The radii of small and large probe spheres are the two parameters that correspond to the "size" and "depth" of the pockets, respectively. These values can be adjusted individual putative ligand molecule. To determine the optimal value of the large probe spheres radius, we generated pockets for thousands of protein structures in the database, using several size of large probe spheres, examined the correspondence of these pockets with known binding site positions. A new measure of shallowness, a minimum inaccessible radius, R(inaccess), indicated that binding sites of coenzymes are very deep, while those for adenine/guanine mononucleotide have only medium shallowness and those for short peptides and oligosaccharides are shallow. The optimal radius of large probe spheres was 3-4 A for the coenzymes, 4 A for adenine/guanine mononucleotides, and 5 A or more for peptides/oligosaccharides. Comparison of our program with two other popular pocket-finding programs showed that our program had a higher performance of detecting binding pockets, although it required more computational time. 相似文献
107.
Hassan M Morimoto S Murakami H Ichiyanagi T Mori N 《Bioscience, biotechnology, and biochemistry》2007,71(6):1439-1446
A new enzyme, NAD+-dependent 4-N-trimethylamino-1-butanol dehydrogenase from Pseudomonas sp. 13CM, was purified 526-fold to apparent homogeneity in 5 chromatographic steps. The enzyme had a molecular mass of 45 kDa and appeared to be a monomer enzyme. The isoeletric point was found to be 4.8. The optimum temperature was 50 degrees C, and the optimum pHs for the oxidation and reduction reactions were 9.5 and 6.0 respectively. The purified enzyme was further characterized with respect to substrate specificity, kinetic parameters, and amino acid terminal sequence. The Km values for trimethylamino-1-butanol and NAD+ were 0.54 mM and 0.22 mM respectively. In the reduction reaction, the apparent Km values for trimethylaminobutylaldehyde and NADH were 0.67 mM and 0.04 mM, respectively. The enzyme was inhibited by SH reagents, chelating reagents, and heavy metal ions. The N-terminal 12 amino acid residues were sequenced. 相似文献
108.
Effects of dietary soybean peptides on hepatic production of ketone bodies and secretion of triglyceride by perfused rat liver 总被引:2,自引:0,他引:2
Tamaru S Kurayama T Sakono M Fukuda N Nakamori T Furuta H Tanaka K Sugano M 《Bioscience, biotechnology, and biochemistry》2007,71(10):2451-2457
Soybean protein isolate (SPI) was digested with protease to produce a peptides containing the low-molecular fraction (LD3) or a mixture of high- and low-molecular fractions (HD1). Rats were fed a diets containing SPI, LD3, or HD1 at a protein level equivalent to the 20% casein diet for 4 weeks. The serum triglyceride concentration was lower in rats fed SPI, LD3, and HD1 diets than in rats fed the casein diet, and the differences were significant for the cholesterol-enriched diet. The value for the LD3 group was the lowest among all groups for both the cholesterol-free and -enriched diets. The level of triglyceride in the post-perfused liver was significantly lower in the LD3 and HD1 groups and the SPI group than in the casein group irrespective of the presence of cholesterol in the diet. In the cholesterol-free diet, LD3 feeding as compared to casein feeding caused a reduction in triglyceride secretion from the liver to perfusate and an increment of hepatic ketone body production. The addition of cholesterol to the diets somewhat attenuated these effects of LD3. These results suggest that the low-molecular fraction in soybean peptides causes triglyceride-lowering activity through a reduction in triglyceride secretion from the liver to the blood circulation and the stimulation of fatty acid oxidation in the liver. There is a possibility that soybean peptides modulate triglyceride metabolism by changes in the hepatic contribution. 相似文献
109.
Takemoto D Takekawa Y Soest RW Fusetani N Matsunaga S 《Bioscience, biotechnology, and biochemistry》2007,71(11):2697-2700
Poecillastrin D (2) was isolated together with poecillastrin C (1) from the deep sea sponge, Japsis serpentina. Its structure was elucidated to be that of a macrolide lactam by spectroscopic methods. These compounds showed potent cytotoxicity against various tumor cell lines. 相似文献