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991.
The reaction of Torulopsis (Candida) utilis 5S ribosomal RNA with kethoxal (beta-ethoxy-alpha-ketobutyraldehyde) was studied in an attempt to identify the exposed guanine residues. At most 7-8 out of 32 guanine residues in T.utilis 5S RNA were kethoxalated after reaction at 37 degrees C for 4 h in the presence of magnesium ions. Localization of the kethoxalated guanine residues in T.utilis 5S RNA was achieved by sequence analyses of RNase T1 digests of the kethoxalated 5S RNA. These analyses showed that residues G37, G57, G91, and some of the three guanine residues G80, G82, and G85, are the most accessible sites. Residues G30, G41, and G49 also reacted with kethoxal though less strongly. These results are for the most part compatible with our secondary structure model for T.utilis 5S 5S RNA (Nishikawa and Takemura (1974) J. Biochem. 76, 935-947). However, partial formation of some hydrogen bonds within the loop region of the model seems to be necessary to explain the inaccessibility of residue G101 to kethoxal. The results are also discussed in comparison with those of similar studies on E.coli 5S RNA. 相似文献
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K Nishikawa 《Nucleic acids symposium series》1986,(17):167-170
Chimeric tRNATyr molecules have been constructed by enzymatic procedures in vitro from the 5'-half fragment of T. utilis tRNATyr and the 3'-half fragment of yeast tRNATyr, and vice versa. These chimeric tRNAs contain base-mismatching(s) in the anticodon stem and, therefore, have only 3 or 4 base pairs in the stem. Although the Tm of these chimeras are largely decreased, there seems to be no gross difference between the structure of native and chimeric tRNATyrs at physiological temperatures in the presence of 10 mM MgCl2. Aminoacylation assays also revealed that the tyrosine-acceptance of the chimeras are fully comparable to that of native tRNATyrs. However, the possibility remains that the properties of the chimeras are considerably different from those of native ones at lower Mg++ concentrations. 相似文献
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Kimiyuki Shibuya Katsumi Kawamine Toru Miura Chiyoka Ozaki Toshiyuki Edano Ken Mizuno Yasunobu Yoshinaka Yoshihiko Tsunenari 《Bioorganic & medicinal chemistry》2018,26(14):4001-4013
We describe our molecular design of aortic-selective acyl-coenzyme A:cholesterol O-acyltransferase (ACAT, also abbreviated as SOAT) inhibitors, their structure–activity relationships (SARs) and their pharmacokinetic (PK) and pharmacological profiles. The connection of two weak ligands—N-(2,6-diisopropylphenyl)acetamide (50% inhibitory concentration [IC50]?=?8.6?μM) and 2-(methylthio)benzo[d]oxazole (IC50?=?31?μM)—via a linker comprising a 6 methylene group chains yielded a highly potent molecule, 9-(benzo[d]oxazol-2-ylthio)-N-(2,6-diisopropylphenyl)nonanamide (3h) that exhibited high potency (IC50?=?0.004?μM) toward aortic ACAT. This head-to-tail design made it possible to markedly enhance the activity to 2150- to 7750-fold and to discriminate the isoform-selectivity based on the double-induced fit mechanism. At doses of 1 and 3?mg/kg, 3h significantly decreased the lipid-accumulation areas in the aortic arch to 74 and 69%, respectively without reducing the plasma total cholesterol level in high fat- and cholesterol-fed F1B hamsters. Here, we demonstrate the antiatherosclerotic effect of 3hin vivo via its direct action on aortic ACAT and its powerful modulator of cholesterol level. This molecule is a potential therapeutic agent for the treatment of diseases involving ACAT-1 overexpression. 相似文献
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Koji Matsuoka Kiyotaka Nishikawa Yusuke Goshu Tetsuo Koyama Ken Hatano Takahiko Matsushita Miho Watanabe-Takahashi Yasuhiro Natori Daiyo Terunuma 《Bioorganic & medicinal chemistry》2018,26(22):5792-5803
Synthetic assembly of sugar moieties and amino acids in order to create “sugar-amino acid hybrid polymers” was accomplished by means of simple radical polymerization of carbohydrate monomers having an amino acid-modified polymerizable aglycon. Amines derived from globotriaoside and lactoside as glycoepitopes were condensed with known carbobenzyloxy derivatives, including Z-Gly, Z-l-Ala and Z-β-Ala, which had appropriate spacer ability and a chiral center to afford fully protected sugar-amino acid hybrid compounds in good yields. After deprotection followed by acryloylation, the water-soluble glycomonomers were polymerized with or without acrylamide in the presence of a radical initiator in water to give corresponding copolymers and homopolymers, which were shown by SEC analysis to have high molecular weights. Evaluation of the biological activities of the glycopolymers against Shiga toxins (Stxs) was carried out, and the results suggested that glycopolymers having highly clustered globotriaosyl residues had high affinity against Stx2 (KD?=?2.7~4.0?µM) even though other glycopolymers did not show any affinity or showed very weak binding affinity. When Stx1 was used for the same assay, all of the glycopolymers having globotriaosyl residues showed high affinity (KD?=?0.30~1.74?µM). Interestingly, couple of glycopolymers having lactosyl moieties had weaker binding affinity against Stx1. In addition, when cytotoxicity assays were carried out for both Stxs, glycopolymers having highly clustered globotriaosyl residues showed higher affinity than that of the copolymers, and only highly clustered-type glycopolymers displayed neutralization potency against Stx2. 相似文献
999.
β‐carotene suppresses Porphyromonas gingivalis lipopolysaccharide‐mediated cytokine production in THP‐1 monocytes cultured with high glucose condition 下载免费PDF全文
Yukari Kajiura Yasufumi Nishikawa Jung Hwan Lew Jun‐ichi Kido Toshihiko Nagata Koji Naruishi 《Cell biology international》2018,42(1):105-111
Periodontitis is associated with development of diabetes mellitus. Although lipopolysaccharide (LPS) of Porphyromonas gingivalis (Pg), a major pathogen of periodontitis, may lead the progression of diabetes complications, the precise mechanisms are unclear. We, therefore, investigated the effects of β‐carotene on production of Pg LPS‐induced inflammatory cytokines in human monocytes cultured high glucose (HG) condition. THP‐1 cells were cultured under 5.5 mM or 25 mM glucose conditions, and cells were stimulated with Pg LPS. To investigate the productivity of TNF‐α, IL‐6, and MCP‐1, cell supernatants were collected for ELISA. To examine the effects of NF‐kB signals on cytokine production, Bay11‐7082 was used. HG enhanced Pg LPS‐induced production of TNF‐α, IL‐6, and MCP‐1 via NF‐kB signals in THP‐1. β‐carotene suppressed the enhancement of the Pg LPS‐induced cytokine production in THP‐1 via NF‐κB inactivation. Our results suggest that β‐carotene might be a potential anti‐inflammatory nutrient for circulating Pg LPS‐mediated cytokine production in diabetic patients with periodontitis. 相似文献
1000.
Monotherapy with a novel intervenolin derivative,AS‐1934, is an effective treatment for Helicobacter pylori infection 下载免费PDF全文