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801.
Xia P Yin ZJ Chen Y Zhang Q Zhang B Xia Y Yang ZY Kilgore N Wild C Morris-Natschke SL Lee KH 《Bioorganic & medicinal chemistry letters》2004,14(12):3341-3343
Two 1-thia-DCK analogues (9a and 9b) were synthesized and evaluated for inhibition of HIV-1 replication in H9 lymphocytes. Compound 9a showed excellent anti-HIV activity with an EC(50) value of 0.00012 microM and therapeutic index of 1408000. Compound 9b was less active with EC(50) and TI values of 3.11 microM and 62.3, respectively. The bioassay results indicated that thia-DCK analogues merit attention as potential HIV-1 inhibitors. 相似文献
802.
Protein sequencing by mass analysis of polypeptide ladders after controlled protein hydrolysis 总被引:4,自引:0,他引:4
The characterization of protein modifications is essential for the study of protein function using functional genomic and proteomic approaches. However, current techniques are not efficient in determining protein modifications. We report an approach for sequencing proteins and determining modifications with high speed, sensitivity and specificity. We discovered that a protein could be readily acid-hydrolyzed within 1 min by exposure to microwave irradiation to form, predominantly, two series of polypeptide ladders containing either the N- or C-terminal amino acid of the protein, respectively. Mass spectrometric analysis of the hydrolysate produced a simple mass spectrum consisting of peaks exclusively from these polypeptide ladders, allowing direct reading of amino acid sequence and modifications of the protein. As examples, we applied this technique to determine protein phosphorylation sites as well as the sequences and several previously unknown modifications of 28 small proteins isolated from Escherichia coli K12 cells. This technique can potentially be automated for large-scale protein annotation. 相似文献
803.
Hahn P Lindsten T Lyubarsky A Ying GS Pugh EN Thompson CB Dunaief JL 《Cell death and differentiation》2004,11(11):1192-1197
Photoreceptors of bax(-/-)bak(-/-) but neither bax(-/-) mice nor bak(-/-) mice are protected from developmental apoptosis, suggesting that bax(-/-)bak(-/-) photoreceptors may also be protected from pathologic apoptosis. To test this possibility, we exposed bax(-/-)bak(-/-) and bax(-/-) mice to bright light, which normally induces photoreceptor death. Photoreceptors in bax(-/-)bak(-/-) mice were protected from death compared to bax(-/-) mice as indicated by a reduction in the number of TUNEL-positive photoreceptor nuclei 24 h following light damage and almost complete preservation of photoreceptors 7 days following light damage. These results provide the first in vivo evidence that combined deficiency of Bax and Bak can rescue cells from a pathologic stimulus more effectively than Bax deficiency and suggest that combined deficiency of Bax and Bak may also protect cells from other insults. 相似文献
804.
Tang YH He Y Yao TW Zeng S 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2004,805(2):249-254
A stereoselective RP-high performance liquid chromatography (HPLC) assay to determine simultaneously the enantiomers of esmolol and its acid metabolite in human plasma was developed. The method involved a solid-phase extraction and a reversed-phase chromatographic separation with UV detection (lambda = 224 nm) after chiral derivatization. 2,3,4,6-tetra-O-acetyl-beta-d-glucopyranosyl isothiocyanate (GITC) was employed as a pre-column chiral derivatization reagent. The assay was linear from 0.09 to 8.0 microg/ml for each enantiomer of esmolol and 0.07-8.0 microg/ml for each enantiomer of the acid metabolite. The absolute recoveries for all enantiomers were >73%. The intra- and inter-day variations were <15%. The validated method was applied to quantify the enantiomers of esmolol and its metabolite in human plasma for hydrolysis studies. 相似文献
805.
Liu CH Wang B Li WZ Yun LH Liu Y Su RB Li J Liu H 《Bioorganic & medicinal chemistry》2004,12(17):4701-4707
A series of 4-alkylamino-1-hydroxymethylimidazo[1,2-a]quinoxalines have been synthesized and evaluated for their adenosine A(1) receptor inhibitory activity in the radioligand binding assays. The compounds were tested for the inhibition percent (IP) and the affinity toward A(1)AR (K(i)) that IP were more than 90% in the nanomolar range. 4-Cyclopentylamino-7,8-dichloro-1-hydroxymethylimidazo[1,2-a]quinoxaline 18 is the most potent compound in this series, having K(i)=7nM, which is remarkably higher than that of IRFI-165 (K(i)=48). 1-Hydroxymethyl groups of the tricyclic heteroarmatic compounds displayed the potent affinities toward A(1)AR. 相似文献
806.
Three new prenylflavonoids, namely corylifols A-C (1-3), together with 13 known ones, were isolated from the seeds of Psoralea corylifolia. Their structures were elucidated by spectral methods including 1D and 2D NMR techniques. All the isolates were tested on antibacterial assays, and nine of them showed significant antibacterial activities against two pathogenic bacteria Staphylococcus aureus and S. epidermidis. The antibacterial structure-activity relationship of these prenylflavonoids (1-16) was also briefly discussed. 相似文献
807.
Mallari JP Choy CJ Hu Y Martinez AR Hosaka M Toriyabe Y Maung J Blecha JE Pavkovic SF Berkman CE 《Bioorganic & medicinal chemistry》2004,12(22):6011-6020
A series of alkyl and aryl phosphonyl, thiophosphonyl, and dithiophosphonyl derivatives of (S)- and (R)-glutamic acid were prepared and examined for inhibitory potency against glutamate carboxypeptidase (carboxypeptidase G). The acquisition of the phosphonamidodithioic acids and the individual phosphonamidothioic acid diastereomers was achieved through a common phosphonamidothiolate precursor, which also allowed for the chromatographic resolution of the chiral phosphorus center of the phosphonamidothioic acids. The most potent inhibitor of the series was the n-butylphosphonamidate derivative of the natural isomer of glutamic acid. Although each diastereomeric pair of three phosphonamidothionates exhibited stereoselective inhibition consistent with the configuration of the chiral phosphorus center, this effect was generally not remarkable. More important, was the effect of carbon stereochemistry upon glutamate carboxypeptidase inhibition as exemplified by a limited series of enantiomeric pairs of phosphonamidate and phosphonamidodithionate derivatives of glutamic acid. The phosphonamidate analogs derived from the unnatural stereoisomer of glutamic acid were devoid of inhibitory potency in contrast to their enantiomers. Surprisingly, the phosphonamidodithionates derived from the unnatural stereoisomer of glutamic acid demonstrated greater inhibitory potency than their naturally-derived antipodes. 相似文献
808.
Anti-AIDS agents. Part 56: Synthesis and anti-HIV activity of 7-thia-di-O-(-)-camphanoyl-(+)-cis-khellactone (7-thia-DCK) analogs 总被引:1,自引:0,他引:1
Chen Y Zhang Q Zhang B Xia P Xia Y Yang ZY Kilgore N Wild C Morris-Natschke SL Lee KH 《Bioorganic & medicinal chemistry》2004,12(24):67-6387
Two thia-DCK analogs (3a,b) were synthesized and evaluated for inhibition of HIV-1 replication in H9 lymphocytes. Compound 3a showed potent anti-HIV activity with an EC50 value of 0.14 μM and a therapeutic index of 1110. However, the corresponding 6-tert-butyl-substituted compound (3b) showed no suppression. The bioassay results indicated that thia-DCK analogs merit attention as potential HIV-1 inhibitors. 相似文献
809.
Intermediate fertile Triticum aestivum (+)Agropyron elongatum somatic hybrids are generated by low doses of UV irradiation 总被引:4,自引:0,他引:4
We report the production and characterization of somatic hybrids between Triticum aestivum L. and Agropyron elongatum (Host) Nevishi (the synonym is Thinopyrum ponticum). Asymmetric protoplast fusion was performed between Agropyron elongatum protoplasts irradiated with a low UV dose and protoplasts of wheat taken from nonregenerable suspension cultures. More than 40 green plantlets were obtained from 15 regenerated clones and one of them produced seeds. The phenotypes of the hybrid plants and seeds were intermediate between wheat and Agropyron elongatum. All of the regenerated calli and plants were verified as intergeneric hybrids on the basis of morphological observation and analysis of isozyme, cytological, 5SrDNA spacer sequences and random amplified polymorphic DNA (RAPD). RFLP analysis of the mitochondrial genome revealed evidence of random segregation and recombination of mtDNA. 相似文献
810.
Lingling?Wang Li?Ma Wenchuan?Leng Jian?Yang Junping?Zhu Jie?Dong Ying?Xue Zhe?Wan Ruoyu?Li Qi?JinEmail author 《中国科学C辑(英文版)》2004,47(5):389-395
Trichophyton rubrum (T. rubrum) is the most common of the superficial fungi. In an effort to better understand the genetic and biochemical makeup ofT. rubrum, we generated cDNA libraries from 3 growth stages and used these to isolate 4002 unique expressed sequence tags (ESTs). Sequence
comparisons with the Genbank database allowed 1226 of the ESTs to be assigned putative functions or matched with homologs
from other organisms. Of the remaining ESTs, 989 were only weakly similar to known sequences and 1787 had no identifiable
functions, suggesting that they represent novel genes. We further analyzed the presence of several important genes involved
in the growth, metabolism, signal transduction, pathogenesis and drug resistance inT. rubrum. This information was used to newly elucidate important metabolic pathways inT. rubrum. Taken together, our results should form the molecular basis for continued research on the physiological processes and pathogenic
mechanisms ofT. rubrum, and may lead to a better understanding of fungal drug resistance and identification of new drug targets. 相似文献