The synthesis of 13- - - -15, 16-dihydroxyprostaglandins

Both pairs of -ll-desoxy- and -13- - -15, 16-dihydroxyprostaglandins have been synthesized via 1,4-conjugate additions of an appropriately functionalized -vinyl cuprate to the requisite cyclopentenone. These prostaglandin analogs are considerably less potent than PGE₂ as gastric secretion inhibitors or as bronchodilators.     

14-3-3 蛋白

介绍了14－3－3蛋白的基本结构和功能,并简要概述了14－3－3蛋白在信号转导,细胞周期调控以及前体蛋白的折叠与运输过程中的作用机理。     

Membrane proteins in Rh+, Rh- and Rh: -29, 38 (- - -/- - -, rh) red cells compared by using SDS-polyacrylamide gel electrophoresis

Since Rh: -29, 38 (- - -/- - -, rh) phenotype of the Rh blood groups (--- in text) revealed unusual red cells, such as stomatocytes and microspherocytes and the relatively shortened half life of 17 days, red cell membrane proteins from Rh + (D), Rh - (d) and --- were compared by using SDS-polyacrylamide gel electrophoresis (SDS-PAGE). No differences were observed among the patterns of the reduced and non-reduced membrane proteins from Rh+, Rh- and --- red cells. Two-dimensional gel electrophoresis of --- red cell membrane proteins also revealed a pattern similar to Rh+ and Rh- red cell membrane proteins. It is suggested that the lack of all Rh antigens causes no visible alteration of red cell membrane proteins detected by the method of Fairbanks G., Steck T.L. and Wallach D.F.H. (1971) Biochemistry, N.Y. 10, 2606-2617.     

Synthesis of protected peptides with the sequence 8-13-1-3 and 4-13-1-3 of mycobacillin and their analogs

We have synthesized both a protected nonapeptide of the mycobacillin 8-13-1-3 amino acid sequence and a protected tridecapeptide of the 4-13-1-3 sequence, which are a fragment and a open chain analog of this antibiotic, respectively. Some of their analogs with a reversed configuration of the amino acids at fixed positions have also been synthesized. The nonapeptides were obtained by coupling partially protected mycobacillin fragments with the sequence 8-10 and 11-13-1-3 while the tridecapeptides were synthesized by coupling partially protected fragments 4-7 and 8-13-1-3. Configuration analogs of these fragments were also used. The coupling methods applied were DCCI/HONSu or DCCI/HOBt. The purification of the synthesized peptides was achieved by means of recrystallization or column chromatography on silica gel. They were characterized mainly by m.p., degree of optical rotation, elemental and amino acid analysis.     

Tiered Assembly of the Yeast Far3-7-8-9-10-11 Complex at the Endoplasmic Reticulum

Target of rapamycin signaling is a conserved, essential pathway integrating nutritional cues with cell growth and proliferation. The target of rapamycin kinase exists in two distinct complexes, TORC1 and TORC2. It has been reported that protein phosphatase 2A (PP2A) and the Far3-7-8-9-10-11 complex (Far complex) negatively regulate TORC2 signaling in yeast. The Far complex, originally identified as factors required for pheromone-induced cell cycle arrest, and PP2A form the yeast counterpart of the STRIPAK complex, which was first isolated in mammals. The cellular localization of the Far complex has yet to be fully characterized. Here, we show that the Far complex localizes to the endoplasmic reticulum (ER) by analyzing functional GFP-tagged Far proteins in vivo. We found that Far9 and Far10, two homologous proteins each with a tail-anchor domain, localize to the ER in mutant cells lacking the other Far complex components. Far3, Far7, and Far8 form a subcomplex, which is recruited to the ER by Far9/10. The Far3-7-8- complex in turn recruits Far11 to the ER. Finally, we show that the tail-anchor domain of Far9 is required for its optimal function in TORC2 signaling. Our study reveals tiered assembly of the yeast Far complex at the ER and a function for Far complex''s ER localization in TORC2 signaling.     

Divergent expression of claudin -1, -3, -4, -5 and -7 in developing human lung

Background

Claudins are the main components of tight junctions, structures which are associated with cell polarity and permeability. The aim of this study was to analyze the expression of claudins 1, 3, 4, 5, and 7 in developing human lung tissues from 12 to 40 weeks of gestation.

Methods

47 cases were analyzed by immunohistochemisty for claudins 1, 3, 4, 5 and 7. 23 cases were also investigated by quantitative RT-PCR for claudin-1, -3 and -4.

Results

Claudin-1 was expressed in epithelium of bronchi and large bronchioles from week 12 onwards but it was not detected in epithelium of developing alveoli. Claudin-3, -4 and -7 were strongly expressed in bronchial epithelium from week 12 to week 40, and they were also expressed in alveoli from week 16 to week 40. Claudin-5 was expressed strongly during all periods in endothelial cells. It was expressed also in epithelium of bronchi from week 12 to week 40, and in alveoli during the canalicular period. RT-PCR analyses revealed detectable amounts of RNAs for claudins 1, 3 and 4 in all cases studied.

Conclusion

Claudin-1, -3, -4, -5, and -7 are expressed in developing human lung from week 12 to week 40 with distinct locations and in divergent quantities. The expression of claudin-1 was restricted to the bronchial epithelium, whereas claudin-3, -4 and -7 were positive also in alveolar epithelium as well as in the bronchial epithelium. All claudins studied are linked to the development of airways, whereas claudin-3, -4, -5 and -7, but not claudin-1, are involved in the development of acinus and the differentiation of alveolar epithelial cells.     

Preparation of alkyl (R)-(-)-3-hydroxybutyrate by acidic alcoholysis of poly-(R)-(-)-3-hydroxybutyrate

An efficient method for the preparation of optically active alkyl (R)-(-)-3-hydroxybutyrates by chemical depolymerization of biopolymer, poly-(R)-(-)-(3-hydroxybutyrate), was established. This method consists of simple recovery of poly-(R)-(-)-(3-hydroxybutyrate) from bacterial cells followed by acidic alcoholysis. When poly-(R)-(-)-(3-hydroxybutyrate) was purified by a simple digestion method that used 0.2 N sodium hydroxide, alkyl (R)-(-)-hydroxybutyrates were most efficiently produced by alcoholysis with anhydrous hydrochloric acid.     

Facile entry to (-)-(R)- and (+)-(S)-mexiletine

The title compounds, 1a and 1b, have been synthesized in a three-step sequence starting from (-)-(S) and (+)-(R)-propylene oxide, respectively, in acceptable overall yields. The enantiomeric excess values for 1a and 1b were 96% and 93% respectively, as assessed by HPLC analysis on a chiral stationary phase of the corresponding N-acetyl derivatives. The synthetic route herein presented may represent a facile entry to highly enriched mexiletine enantiomers, alternative to those previously reported in the literature.     

alpha,beta-Dibenzyl-gamma-butyrolactone lignan alcohols: total synthesis of (+/-)-7'-hydroxyenterolactone, (+/-)-7'-hydroxymatairesinol and (+/-)-8-hydroxyenterolactone

Two trans-alpha,beta-dibenzyl-gamma-butyrolactone lignans carrying a hydroxyl group at the beta-benzylic carbon atom and a alpha-hydroxy alpha,beta-dibenzyl-gamma-butyrolactone lignan were synthesized in racemic form using the tandem conjugate addition reaction to construct the basic lignan skeleton. Subsequent reaction steps involved either a catalytic reduction of the regenerated keto group to the alcohol, or a hydrogenolysis to benzylic methylene followed by lactone enolate formation and oxidation to give the alpha-hydroxybutyrolactones. These procedures were applied for the synthesis of 7'-hydroxyenterolactones and 7'-hydroxymatairesinols, and 8-hydroxyenterolactones, respectively. The diastereomeric mixtures of these compounds were separated either by HPLC techniques or column chromatography and the structures were elucidated using NMR spectroscopy.     

35-10-9.pdf

The microtubule organizational changes in the isolated generative cells of Allemanda schottii were followed using immunofluorescence and confocal laser scanning microscopy. Due to the improved resolution and the lack of out-of-focus flares, the microtubule cytoskeleton of the generative cells could be visualized more clearly than using conventional epifluorescence systems. Immediately after isolation the microtubule cytoskeleton of the generative cells was cage-like composed of longitudinally oriented microtubule bundles. Later, some bundles began to depolymerize and at the same time some smaller bundles appearred. The smaller bundles unlike the longitudinal bundles crisscrossed throughout the cell. Later still, the cells became spherical. Both the longitudinal and the smaller bundles disappearred. At the same time some of the microtubules began to aggregate around the nucleus. These perinuclear microtubules were apparently not very stable, because soon afterwards,they started to disintegrate. By the time the cells became completely spherical,the cytoplasm became filled with diffuse fluorescence indicating that the tubulin was no longer existing in a polymerized form but in a monomeric form inside the cell. After the fuberlin had completely depolymerized the microtubules started to reform. The sequence of events leading to the reformation of the microtubule cytoskeleton in the spherical cells was as follow: A few nucleating centres began to form first. Then the nucleating centres gave rise to microtubule bundles. The bundles extended and aggregated to form a reticulate network. This cytoskeletal network appearred stable and well organized. It also had a lot of microtubule-bundle junctions. The network persisted after Triton X-l00 extraction.