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81.
The dependence of protein synthesis on the intracellular content of aminoacylated tRNA has been studied in mouse ascites tumor cells deprived for various amino acids. A remarkable reduction in net protein synthesis has been found only after a drastic decrease in aminoacylation of tRNA. The quantitative correlation of protein synthesis with the degree of aminoacylation suggests that a moderate amino acid starvation primarily influences the rate of elongation at the codon concerned. These results are in contrast to the findings previously reported for HeLa cells. Some crucial steps during the determination of intracellular aminoacyl-tRNA have been investigated. The reliability of the method employed has been discussed on a theoretical basis. 相似文献
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Fluoromethylcyclopropylamine derivatives as potential in vivo toxicophores – A cautionary disclosure
Ben Acton Helen F. Small Kate M. Smith Alison McGonagle Alexandra I.J. Stowell Dominic I. James Niall M. Hamilton Nicola Hamilton James R. Hitchin Colin P. Hutton Ian D. Waddell Donald J. Ogilvie Allan M. Jordan 《Bioorganic & medicinal chemistry letters》2019,29(4):560-562
Fluorination of metabolic hotspots in a molecule is a common medicinal chemistry strategy to improve in vivo half-life and exposure and, generally, this strategy offers significant benefits. Here, we report the application of this strategy to a series of poly-ADP ribose glycohydrolase (PARG) inhibitors, resulting in unexpected in vivo toxicity which was attributed to this single-atom modification. 相似文献
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Humphries PS Almaden JV Barnum SJ Carlson TJ Do QQ Fraser JD Hess M Kim YH Ogilvie KM Sun S 《Bioorganic & medicinal chemistry letters》2006,16(23):6116-6119
A series of novel pyridine-2-propanoic acids was synthesized. A structure-activity relationship study of these compounds led to the identification of potent dual PPARalpha/gamma agonists with varied isoform selectivity. Based on the results of efficacy studies in diabetic (db/db) mice, and the desired pharmacokinetic parameters, compound (S)-13 was selected for further profiling. 相似文献
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Ballard P Bradbury RH Harris CS Hennequin LF Hickinson M Kettle JG Kendrew J Klinowska T Ogilvie DJ Pearson SE Williams EJ Wilson I 《Bioorganic & medicinal chemistry letters》2006,16(18):4908-4912
The structure-activity and structure-property relationships of anilinoquinazoline inhibitors of EGFR were investigated. Strategies to lower volume of distribution and shorten half-life through structure and pKa modulation are discussed. 相似文献
89.
Vargas ML Cruickshank RH Ross JG Holyoake AJ Ogilvie SC Paterson AM 《Molecular ecology resources》2009,9(2):505-515
The brushtail possum is a major agricultural and ecological pest in New Zealand. A novel noninvasive DNA sampling tool for detecting its presence (WaxTags, or WT) was tested. DNA was recovered from saliva left on WT, and two lengths (407 bp and 648 bp) of the cytochrome c oxidase I (COI) barcoding region were amplified by polymerase chain reaction (PCR). PCR products were considered (+) when a DNA band was clearly visible by electrophoresis. Different factors that might affect PCR (+) were investigated with captive possums: (i) both extraction protocols of the QIAGEN DNeasy Blood and Tissue Kit, (ii) effect of an overnight or longer delay of up to 3 weeks before DNA extraction on both COI amplicons, and (iii) effect of the individual, order and magnitude of the bite. Extraction protocols were not significantly different. The effect of the overnight delay was not significant, and amplification of the short amplicon was significantly higher (100%) than for the long fragment (48%). After a two or 3‐week delay, the short amplicon had 94% and 56% PCR (+), success rates, respectively. Individual, order and magnitude of a bite had no significant effect. The delay trial was repeated with WT from the wild, for which PCR (+) rate of the short amplicon was 63%, regardless of freshness. Four microsatellites were amplified from captive WT samples. We conclude that DNA from saliva traces can be recovered from WT, a potential new tool for noninvasive monitoring of possums and other wildlife. 相似文献
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