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991.
Onodera H Kaneko M Takahashi Y Uochi Y Funahashi J Nakashima T Soga S Suzuki M Ikeda S Yamashita Y Rahayu ES Kanda Y Ichimura M 《Bioorganic & medicinal chemistry letters》2008,18(5):1588-1591
Hsp90 is an attractive chemotherapeutic target because it is essential to maturation of multiple oncogenes. We describe the conformational significance of EH21A1-A4, phenolic derivatives of geldanamycin isolated from Streptomyces sp. Their native free structures are similar to the active form of geldanamycin bound to Hsp90 protein. Their conformational character is a probable reason for their high-affinity binding. Lack of toxic benzoquinone in EH21A1-A4 also adds to their potential as lead compounds for anti-tumor drugs. 相似文献
992.
Moree WJ Kataoka K Ramirez-Weinhouse MM Shiota T Imai M Tsutsumi T Sudo M Endo N Muroga Y Hada T Fanning D Saunders J Kato Y Myers PL Tarby CM 《Bioorganic & medicinal chemistry letters》2008,18(6):1869-1873
SAR studies were conducted around lead compound 1 using high-throughput parallel solution and solid phase synthesis. Our lead optimization efforts led to the identification of several CCR2b antagonists with potent activity in both binding and functional assays [Compound 71 CCR2b Binding IC(50) 3.2 nM; MCP-1-Induced Chemotaxis IC(50) 0.83 nM; Ca(2+) Flux IC(50) 7.5 nM]. 相似文献
993.
Aoki K Kiyokawa E Nakamura T Matsuda M 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2008,363(1500):2143-2151
Fluorescence probes based on the principle of Förster resonance energy transfer (FRET) have shed new light on our understanding of signal transduction cascades. Among them, unimolecular FRET probes containing fluorescence proteins are rapidly increasing in number because these genetically encoded probes can be easily loaded into living cells and allow simple acquisition of FRET images. We have developed probes for small GTPases, tyrosine kinases, serine–threonine kinases and phosphoinositides. Images obtained with these probes have revealed that membrane protrusions such as nascent lamellipodia or neurites provide an active signalling platform in the growth factor-stimulated cells. 相似文献
994.
Wen XP Pang XM Matsuda N Kita M Inoue H Hao YJ Honda C Moriguchi T 《Transgenic research》2008,17(2):251-263
An apple spermidine synthase (SPDS) gene (MdSPDS1) was verified to encode a functional protein by the complementation of the spe3 yeast mutant, which lacks the SPDS gene. To justify our hypothesis that apple SPDS is involved in abiotic stress responses and to obtain transgenic fruit trees
tolerant to abiotic stresses as well, MdSPDS1-over-expressing transgenic European pear (Pyrus communis L. ‘Ballad’) plants were created by Agrobacterium-mediated transformation. A total of 21 transgenic lines showing various spermidine (Spd) titers and MdSPDS1 expression levels were obtained. Selected lines were exposed to salt (150 mM NaCl), osmosis (300 mM mannitol), and heavy
metal (500 μM CuSO4) stresses for evaluating their stress tolerances. Transgenic line no. 32, which was revealed to have the highest Spd accumulation
and expression level of MdSPDS1, showed the strongest tolerance to these stresses. When growth increments, electrolyte leakage (EL), and values of thiobarbituric
acid reactive substances (TBARS) were monitored, line no. 32 showed the lowest growth inhibition and the least increase in
EL or TBARS under stress conditions. Spd titers in wild-type and transgenic lines showed diverse changes upon stresses, and
these changes were not consistent with the changes in MdSPDS1 expressions. Moreover, there were no differences in the sodium concentration in the shoots between the wild type and line
no. 32, whereas the copper concentration was higher in the wild type than in line no. 32. Although the mechanism(s) underlying
the involvement of polyamines in stress responses is not known, these results suggest that the over-expression of the SPDS gene substantially increased the tolerance to multiple stresses by altering the polyamine titers in pear. Thus, MdSPDS1-over-expressing transgenic pear plants could be used to improve desert land and/or to repair polluted environments.
Xiao-Peng Wen and Xiao-Ming Pang contributed equally to this work. 相似文献
995.
Yamaguchi K Kazuta Y Hirano K Yamada S Matsuda A Shuto S 《Bioorganic & medicinal chemistry》2008,16(19):8875-8881
A series of the cyclopropane-based conformationally restricted analogs of haloperidol were designed as potential antidopaminergic agents and were effectively synthesized using highly stereoselective Grignard reaction with tert-butanesulfinyl imines as the key step. Pharmacological evaluation of the compounds showed that the conformational restriction method can effectively work for improving the pharmacological selectivity of a parent compound and also for investigating the bioactive conformation. 相似文献
996.
Itoh T Ito Y Ohguchi K Ohyama M Iinuma M Otsuki Y Nozawa Y Akao Y 《Bioorganic & medicinal chemistry》2008,16(2):721-731
Eupalinin A, a natural phytoalexin included in Eupatorium chinense L., exhibited a marked inhibitory effect on cell growth in HL60 cells. The morphological aspects of eupalinin A-treated cells evaluated by Hoechst 33342 nuclear staining indicated cell death, only a small part of which showed a typical apoptosis with nuclear fragmentation and condensation. To determine what type of cell death is caused by eupalinin A, we examined the contribution of caspases, Bcl-2 family proteins, MAP kinase, and PI3K/Akt, and mitochondrial membrane potential to this cell death. As a result, most part of the cell death was not associated with apoptosis because of caspase independence and no death factor released from mitochondria. Electron microscopic study indicated a characteristic finding of autophagy such as the formation of autophagosomes. Furthermore, the level of microctubule-associated-protein light chain 3 (LC3) II protein and monodancylcanaverin (MDC) incorporation were gradually increased with reduction of mitochondrial membrane potential by the accumulation of intracellular ROS after eupalinin A treatment. From these results, we can conclude that eupalinin A-induced cell death was mainly due to autophagy, which was initiated by increased ROS, resulting in the perturbation of mitochondrial membrane potential. Since the class III PI3K inhibitor such as 3-MA or LY294002 did not inhibit the eupalinin A-induced type II programmed cell death (PCD II), it was suggested that the PCD II was executed by Beclin-1 independent pathway of damage-induced mitochondrial autophagy (mitophagy). 相似文献
997.
Hirokazu Yamada Masatoshi Tomaru Muneo Matsuda Yuzuru Oguma 《Journal of Insect Behavior》2008,21(4):222-239
Drosophila ananassae and D. pallidosa are closely related, sympatric species that lack postmating isolation. Sexual isolation has been considered important in
maintaining them as independent species. To clarify the behavioral processes leading to sexual isolation, we analyzed behavioral
sequences and examined the effect of courtship song on mating success and on behaviors of both sexes by surgically removing
male wings (song generators), female aristae (song receivers), or female wings (means of fluttering). We found that heterospecific
courtship songs evoked female wing fluttering, whereas conspecific courtship song did not. Furthermore, female wing fluttering
made courting males discontinue courtship. These findings suggest that strong sexual isolation is achieved through the following
behavioral sequence: heterospecific song→female wing fluttering→courtship discontinuation. 相似文献
998.
Matsubara T Aoki N Honjoh T Mizumachi K Kurisaki J Okajima T Nadano D Matsuda T 《Bioscience, biotechnology, and biochemistry》2008,72(10):2555-2565
Intestinal absorption of food proteins is well known, whereas its physiological significance remains to be investigated. Various amounts (1, 10 and 50 mg) of ovalbumin were orally administered to mice and the blood kinetics were subsequently analyzed by two-site ELISA. The blood ovalbumin concentration consistently reached its maximum (7-90 ng/ml) about 20 min after the oral administration and then gradually decreased in a dose-dependent manner. Only intact (45 kDa) and truncated (40 kDa) ovalbumins were always detected in the blood independently of the administration site, intra-stomach or intra-intestine, while various fragments of the protein were observed in the gastrointestinal lumen after the oral administration. Recognition by a specific monoclonal antibody and an acidic shift of its pI value suggested that the 40-kDa truncated ovalbumin was produced by intracellular limited proteolysis at its C-terminus. Such stable absorption and blood kinetics of undigested ovalbumin in normal mice suggest some sort of physiological significance for the intestinal uptake of intact food proteins. 相似文献
999.
Shibayama H Hisama M Matsuda S Kawase A Ohtsuki M Hanada K Iwaki M 《Bioscience, biotechnology, and biochemistry》2008,72(4):1015-1022
The novel amphiphilic vitamin C derivative disodium isostearyl 2-O-L-ascorbyl phosphate (VCP-IS-2Na), which has a C(18) alkyl chain attached to the stable ascorbate derivative sodium L-ascorbic acid 2-phosphate (VCP-Na), was evaluated for reduction of cell damage induced by oxidative stress, ultraviolet A (UVA), ultraviolet B (UVB), and H(2)O(2); stimulation of collagen synthesis against UVA irradiation; and inhibition of matrix metalloproteinase-1 (MMP-1) activity induced by UVA in human normal dermal fibroblasts. VCP-IS-2Na pretreatment resulted in significant protection against cell damage induced by UVB, UVA, and H(2)O(2). The amount of type I collagen following UVA irradiation was increased by treatment with VCP-IS-2Na in a concentration-dependent manner. These effects of VCP-IS-2Na were superior to those of L-ascorbic acid (vitamin C, VC) and VCP-Na. On the other hand, VCP-IS-2Na suppressed 65% of the excess MMP-1 irradiated UVA, and VC and VCP-Na slightly suppressed it. 相似文献
1000.
Osamu Sato Satoshi Miura Hiroyuki Maruyama Yanjuan Zhang Dayu Wu Wen Zhang Haitao Xu Ryotaro Matsuda Haoling Sun Jun Tao 《Inorganica chimica acta》2008,361(12-13):3659-3662
The magnetic and photo-magnetic properties of Co dinuclear compounds were studied. The Co compounds, [{Co(tpa)}2(dhbq)](BF4)3 · 2H2O and [{Co(tpa)}2(dhbq)](ClO4)3 · 2H2O, have the structure [(tpa)CoIII-LS–(μ-dhbq)3?–CoIII-LS(tpa)]3? (where LS, H2dhbq, tpa denote low-spin, 2,5-di-hydroxy-1,4-benzoquinone and tris(2-pyridylmethyl)amine, respectively) at room temperature. On heating, these compounds exhibit valence-tautomeric inter-conversion; [(tpa)CoIII-LS–(μ-dhbq)3?–CoIII-LS(tpa)]3? ? [(tpa)CoII-HS–(μ-dhbq)2?–CoIII-LS(tpa)]3? (where HS denotes high-spin). Furthermore, both of these compounds exhibit photo-induced valence tautomerism at low temperature (<60 K). These results show that the electronic structures of these complexes can be controlled by modifying the counter anions. 相似文献