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141.
Kazumi Kajiwara Kentaro Watanabe Rei Tokiwa Tomoko Kurose Hiroaki Ohno Hiroko Tsutsumi Yoji Hata Kazuki Izumi Eiichi Kodama Masao Matsuoka Shinya Oishi Nobutaka Fujii 《Bioorganic & medicinal chemistry》2009,17(23):7964-7970
The bioorganic synthesis of an end-capped anti-HIV peptide from a recombinant protein was investigated. Cyanogen bromide-mediated cleavage of two Met-Gln sites across the target anti-HIV sequence generated an HIV-1 fusion inhibitor (SC35EK) analog bearing an N-terminal pyroglutamate (pGlu) residue and a C-terminal homoserine lactone (Hsl) residue. The end-capped peptide, pGlu-SC35EK-Hsl, had similar bioactivity and biophysical properties to the parent peptide, and an improved resistance to peptidase-mediated degradation was observed compared with the non-end-capped peptide obtained using standard recombinant technology. 相似文献
142.
Nishikawa H Nakamura S Kodama E Ito S Kajiwara K Izumi K Sakagami Y Oishi S Ohkubo T Kobayashi Y Otaka A Fujii N Matsuoka M 《The international journal of biochemistry & cell biology》2009,41(4):891-899
Alpha-helical peptides, such as T-20 (enfuvirtide) and C34, derived from the gp41 carboxyl-terminal heptad repeat (C-HR) of HIV-1, inhibit membrane fusion of HIV-1 and the target cells. Although T-20 effectively suppresses the replication of multi-drug resistant HIV variants both in vitro and in vivo, prolonged therapy with T-20 induces emergence of T-20 resistant variants. In order to suppress the emergence of such resistant variants, we introduced charged and hydrophilic amino acids, glutamic acid (E) and lysine (K), at the solvent accessible site of C34. In particular, the modified peptide, SC34EK, demonstrates remarkably potent inhibition of membrane fusion by the resistant HIV-1 variants as well as wild-type viruses. The activity was specific to HIV-1 and little influenced by serum components. We found a strong correlation between the anti-HIV-1 activities of these peptides and the thermostabilities of the 6-helix bundles that are formed with these peptides. We also obtained the crystal structure of SC34EK in complex with a 36 amino acid sequence (N36) comprising the amino-terminal heptad repeat of HIV-1. The EK substitutions in the sequence of SC34EK were directed toward the solvent and generated an electrostatic potential, which may result in enhanced alpha-helicity of the peptide inhibitor. The 6-helix bundle complex of SC34EK with N36 appears to be structurally similar to that of C34 and N36. Our approach to enhancing alpha-helicity of the peptide inhibitor may enable future design of highly effective and specific HIV-1 inhibitors. 相似文献
143.
Ishida Norio K. Uchida Daisuke Doi Ryosuke Oishi Katsutaka Chikahisa Sachiko Sei Hiroyoshi Hamasaka Yasutaka Suzuki Takahiro Hanai Shuji 《Sleep and biological rhythms》2010,8(1):2-8
Sleep and Biological Rhythms - In nature, hibernating animals experience fasting, cold temperature, and short day seasonally. Torpor is a state of decreased physiological activity in an animal,... 相似文献
144.
Niida A Wang Z Tomita K Oishi S Tamamura H Otaka A Navenot JM Broach JR Peiper SC Fujii N 《Bioorganic & medicinal chemistry letters》2006,16(1):134-137
Metastin has been identified as a metastasis suppressor gene product that mediates its function through a G protein coupled receptor, GPR54. To refine insight into the critical pharmacophore for the activation of GPR54, we have conducted alanine and d-amino acid scanning on a biologically active metastin fragment (45-54). Based on these data and structures of peptides previously reported to activate GPR54, a series of shortened metastin (45-54) derivatives were synthesized and tested for the ability to induce GPR54 signaling. These biological experiments were performed in yeast containing human GPR54 that was coupled to the pheromone response pathway and a pheromone responsive lacZ reporter gene. Compounds 32, 33, and 39, which possess an N-terminal basic group and a C-terminal RW-amide motif, were strong agonists, similar to the level of metastin. This may provide an approach to reverse the pro-metastatic effect of metastin deletion in multiple malignant tumors. 相似文献
145.
Anqi Qiu Kenichi Oishi Michael I. Miller Constantine G. Lyketsos Susumu Mori Marilyn Albert 《PloS one》2010,5(3)
Background
White matter disruption has been suggested as one of anatomical features associated with Alzheimer''s disease (AD). Diffusion tensor imaging (DTI), which has been widely used in AD studies, obtains new insights into the white matter structure.Methods
We introduced surface-based geometric models of the deep white matter tracts extracted from DTI, allowing the characterization of their shape variations relative to an atlas as well as fractional anisotropy (FA) variations on the atlas surface through large deformation diffeomorphic metric mapping (LDDMM). We applied it to assess local shapes and FA variations of twenty-three deep white matter tracts in 13 patients with AD and 19 healthy control subjects.Results
Our results showed regionally-specific shape abnormalities and FA reduction in the cingulum tract and the sagittal stratum tract in AD, suggesting that disruption in the white matter tracts near the temporal lobe may represent the secondary consequence of the medial temporal lobe pathology in AD. Moreover, the regionally-specific patterns of FA and shape of the white matter tracts were shown to be of sufficient sensitivity to robustly differentiate patients with AD from healthy comparison controls when compared with the mean FA and volumes within the regions of the white matter tracts. Finally, greater FA or deformation abnormalities of the white matter tracts were associated with lower MMSE scores.Conclusion
The regionally-specific shape and FA patterns could be potential imaging markers for differentiating AD from normal aging. 相似文献146.
Asami Y Oishi J Kitazaki H Kamimoto J Kang JH Niidome T Mori T Katayama Y 《Analytical biochemistry》2011,(1):1628-49
Here we developed a simple set-and-mix assay to perform high-throughput screening of protein kinase A (PKA) inhibitors from the LOPAC 1280 compound library. This assay is based on the color change of gold nanoparticles on aggregation induced by a cationic substrate peptide as coagulant. In spite of the simplicity of this assay system, this assay can be applied to drug screening based on cellular kinases. We successfully found several highly active inhibitors, including compounds that have not been reported before. 相似文献
147.
Yoshiyuki Tohno Setsuko Tohno Takao Oishi Takeshi Minami Pongsak Khanpetch Cho Azuma Ranida Quiggins 《Biological trace element research》2014,161(1):78-84
To elucidate compositional changes of the ligament with aging, the authors investigated age-related changes of elements in the ligamentum capitis femoris (LCF) of monkeys with a wide range of ages by direct chemical analysis. Used rhesus and Japanese monkeys consisted of 9 males and 22 females, ranging in age from newborn to 31 years (average age?=?10.4?±?10.9 years). After incineration with nitric acid and perchloric acid, element contents were determined by inductively coupled plasma-atomic emission spectrometry. It was found that the P content decreased significantly in the LCFs of monkeys with aging, but other six element contents, Ca, S, Mg, Zn, Fe, and Na, did not change significantly with aging. Assuming that the P content indicated the active cell density and the S content indicated the protein amount, an age-related change of the mass ratio of P/S was examined in the LCFs. The mass ratio of P/S decreased significantly in the LCFs in childhood. Regarding the relationships among elements, significant direct correlations were found among the Ca, P, S, and Mg contents in the LCFs. It was suggested that the active cell density of the connective tissue cells might decrease significantly in the LCF in childhood. 相似文献
148.
Masayuki Hata Kazuaki Miyamoto Akio Oishi Yukiko Makiyama Norimoto Gotoh Yugo Kimura Tadamichi Akagi Nagahisa Yoshimura 《PloS one》2014,9(11)
Objectives
To compare the optic nerve head (ONH) structure between compressive optic neuropathy (CON) and glaucomatous optic neuropathy (GON), and to determine whether selected ONH quantitative parameters effectively discriminate between GON and CON, especially CON cases presenting with a glaucoma-like disc.Methods
We prospectively assessed 34 patients with CON, 34 age-matched patients with moderate or severe GON, and 34 age-matched healthy control subjects. The quantitative parameters of ONH structure were compared using the Heidelberg Retina Tomograph 2 (HRT2) and Spectralis optical coherence tomography with an enhanced depth imaging method.Results
The mean and maximum cup depths of CON were significantly smaller than those with GON (P<0.001 and P<0.001, respectively). The distance between Bruch''s membrane opening and anterior surface of the lamina cribrosa (BMO-anterior LC) of CON was also significantly smaller than that of glaucoma but was similar to that of the healthy group (P<0.001 and P = 0.47, respectively). Based on Moorfields regression analysis of the glaucoma classification of HRT2, 15 eyes with CON were classified with a glaucoma-like disc. The cup/disc area ratio did not differ between cases of CON with a glaucoma-like disc and cases of GON (P = 0.16), but the BMO-anterior LC and mean and maximum cup depths of CON cases with a glaucoma-like disc were smaller than those in GON (P = 0.005, P = 0.003, and P = 0.001, respectively).Conclusions
Measurements of the cup depths and the LC depth had good ability to differentiate between CON with a glaucoma-like disc and glaucoma. There was no laminar remodeling detected by laminar surface position in the patients with CON compared to those with GON. 相似文献149.
Tomoya Hirose Shigeto Hamaguchi Naoya Matsumoto Taro Irisawa Masafumi Seki Osamu Tasaki Hideo Hosotsubo Norihisa Yamamoto Kouji Yamamoto Yukihiro Akeda Kazunori Oishi Kazunori Tomono Takeshi Shimazu 《PloS one》2014,9(11)
Neutrophil extracellular traps (NETs), a newly identified immune mechanism, are induced by inflammatory stimuli. Modification by citrullination of histone H3 is thought to be involved in the in vitro formation of NETs. The purposes of this study were to evaluate whether NETs and citrullinated histone H3 (Cit-H3) are present in the bloodstream of critically ill patients and to identify correlations with clinical and biological parameters. Blood samples were collected from intubated patients at the time of ICU admission from April to June 2011. To identify NETs, DNA and histone H3 were visualized simultaneously by immunofluorescence in blood smears. Cit-H3 was detected using a specific antibody. We assessed relationships of the presence of NETs and Cit-H3 with the existence of bacteria in tracheal aspirate, SIRS, diagnosis, WBC count, and concentrations of IL-8, TNF-α, cf-DNA, lactate, and HMGB1. Forty-nine patients were included. The median of age was 66.0 (IQR: 52.5–76.0) years. The diagnoses included trauma (7, 14.3%), infection (14, 28.6%), resuscitation from cardiopulmonary arrest (8, 16.3%), acute poisoning (4, 8.1%), heart disease (4, 8.1%), brain stroke (8, 16.3%), heat stroke (2, 4.1%), and others (2, 4.1%). We identified NETs in 5 patients and Cit-H3 in 11 patients. NETs and/or Cit-H3 were observed more frequently in “the presence of bacteria in tracheal aspirate” group (11/22, 50.0%) than in “the absence of bacteria in tracheal aspirate” group (4/27, 14.8%) (p<.01). Multiple logistic regression analysis showed that only the presence of bacteria in tracheal aspirate was significantly associated with the presence of NETs and/or Cit-H3. The presence of bacteria in tracheal aspirate may be one important factor associated with NET formation. NETs may play a pivotal role in the biological defense against the dissemination of pathogens from the respiratory tract to the bloodstream in potentially infected patients. 相似文献
150.