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Elisabetta Colletti Laura Frontali Claudio Palleschi Micheline Wesolowski Hiroshi Fukuhara 《Molecular & general genetics : MGG》1979,175(1):1-4
Summary In S. cerevisiae four isoacceptor mitochondrial tRNAs for serine have been separated by reversed phase chromatography. At least two of these species are products of different genes. In this work the deletion mapping technique has been used to locate two genes for tRNAser. The gene for tRNAser previously localized in the oli I region of the mitochondrial genome has been found to code for tRNA
ser
2
, and another gene coding for tRNA
ser
1
has been detected in the region where most of other tRNA genes are found. Results of fine mapping experiments allowed to localize this gene in the proximity of the gene for tRNAarg. 相似文献
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Chad Sanada Chung‐Jung Kuo Evan J. Colletti Melisa Soland Saloomeh Mokhtari Mary Ann Knovich John Owen Esmail D. Zanjani Christopher D. Porada Graça Almeida‐Porada 《Journal of cellular physiology》2013,228(5):1010-1016
Besides the liver, it has been difficult to identify which organ(s) and/or cellular component(s) contribute significantly to the production of human FVIII:c (FVIII). Thus far, only endothelial cells have been shown to constitute a robust extrahepatic source of FVIII, possibly explaining both the diverse presence of FVIII mRNA in the body, and the observed increase in FVIII levels during liver failure. Here, we investigate whether human mesenchymal stem cells (MSC), ubiquitously present in different organs, could also contribute to FVIII production. MSC isolated from human lung, liver, brain, and bone marrow expressed FVIII message as determined by quantitative‐RT‐PCR. Using an antibody specific for FVIII, confocal microscopy, and umbilical cord‐derived endothelial cells (HUVEC) as a negative control, we demonstrated that, in MSC, FVIII protein was not stored in granules; rather, it localized to the perinuclear region. Furthermore, functional FVIII was detected in MSC supernatants and cell lysates by aPTT and chromogenic assays. These results demonstrate that MSC can contribute at low levels to the functional FVIII pool, and advance the understanding of the physiology of FVIII production and secretion. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc. 相似文献
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Shen HC Szymonifka MJ Kharbanda D Deng Q Carballo-Jane E Wu KK Wu TJ Cheng K Ren N Cai TQ Taggart AK Wang J Tong X Waters MG Hammond ML Tata JR Colletti SL 《Bioorganic & medicinal chemistry letters》2007,17(24):6723-6728
A urea class of high affinity niacin receptor agonists was discovered. Compound 1a displayed good PK, better in vivo efficacy in reducing FFA in mouse than niacin, and no vasodilation in a mouse model. Compound 1q demonstrated equal affinity to GPR109A as niacin. 相似文献
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Raghavan S Tria GS Shen HC Ding FX Taggart AK Ren N Wilsie LC Krsmanovic ML Holt TG Wolff MS Waters MG Hammond ML Tata JR Colletti SL 《Bioorganic & medicinal chemistry letters》2008,18(11):3163-3167
The design, synthesis, and biological activity of a series of cycloalkene acid-based niacin receptor agonists are described. This led to the discovery that tetrahydro anthranilic acid is an excellent surrogate for anthranilic acid. Several compounds were identified that were potent against the niacin receptor, had enhanced cytochrome P450 selectivity against subtypes CYP2C8 and CYP2C9, and improved oral exposure in mice. 相似文献
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Hong C. Shen Fa-Xiang Ding Sheo B. Singh Gopalakrishnan Parthasarathy Stephen M. Soisson Sookhee N. Ha Xun Chen Srinivas Kodali Jun Wang Karen Dorso James R. Tata Milton L. Hammond Malcolm MacCoss Steven L. Colletti 《Bioorganic & medicinal chemistry letters》2009,19(6):1623-1627
Platensimycin (1) displays antibacterial activity due to its inhibition of the elongation condensing enzyme (FabF), a novel mode of action that could potentially lead to a breakthrough in developing a new generation of antibiotics. The medicinal chemistry efforts were focused on the modification of the enone moiety of platensimycin and several analogs showed significant activity against FabF and possess antibacterial activity. 相似文献
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Hong C. Shen Fa-Xiang Ding Siyi Wang Suoyu Xu Hsuan-shen Chen Xinchun Tong Vincent Tong Kaushik Mitra Sanjeev Kumar Xiaoping Zhang Yuli Chen Gaochao Zhou Lee-Yuh Pai Magdalena Alonso-Galicia Xiaoli Chen Bei Zhang James R. Tata Joel P. Berger Steven L. Colletti 《Bioorganic & medicinal chemistry letters》2009,19(13):3398-3404
Spirocyclic secondary amine-derived trisubstituted ureas were identified as highly potent, bioavailable and selective soluble epoxide hydrolase (sEH) inhibitors. Despite good oral exposure and excellent ex vivo target engagement in blood, one such compound, rac-1a, failed to lower blood pressure acutely in spontaneously hypertensive rats (SHRs). This study posed the question as to whether sEH inhibition provides a robust mechanism leading to a significant antihypertensive effect. 相似文献
9.
Colletti PF Goyal Y Varman AM Feng X Wu B Tang YJ 《Biotechnology and bioengineering》2011,108(4):893-901
In the production of chemicals via microbial fermentation, achieving a high yield is one of the most important objectives. We developed a statistical model to analyze influential factors that determine product yield by compiling data obtained from engineered Escherichia coli developed within last 10 years. Using both numerical and ordinal variables (e.g., enzymatic steps, cultivation conditions, and genetic modifications) as input parameters, our model revealed that cultivation modes, nutrient supplementation, and oxygen conditions were the three significant factors for improving product yield. Generally, the model showed that product yield decreases as the number of enzymatic steps in the biosynthesis pathway increases (7-9% loss of yield per enzymatic step). Moreover, overexpression of enzymes or removal of competitive pathways (e.g., knockout) does not necessarily result in an amplification of product yield (P-value>0.1), possibly because of limited capacity in the biosynthesis pathway to accommodate an increase in flux. The model not only provides general guidelines for metabolic engineering and fermentation processes, but also allows a priori estimation and comparison of product yields under designed cultivation conditions. 相似文献
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Kopka IE Lin LS Mumford RA Lanza T Magriotis PA Young D DeLaszlo SE MacCoss M Mills SG Van Riper G McCauley E Lyons K Vincent S Egger LA Kidambi U Stearns R Colletti A Teffera Y Tong S Owens K Levorse D Schmidt JA Hagmann WK 《Bioorganic & medicinal chemistry letters》2002,12(17):2415-2418
A series of substituted N-(3,5-dichlorobenzenesulfonyl)-(L)-prolyl- and (L)-azetidyl-beta-biaryl beta-alanine derivatives was prepared as selective and potent VLA-4 antagonists. The 2,6-dioxygenated biaryl substitution pattern is important for optimizing potency. Oral bioavailability was variable and may be a result of binding to circulating plasma proteins. 相似文献