| Effect of polyamine analogues on hypusine content in JURKAT T-cells. | |
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MedLine Citation:
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PMID: 9748365 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The availability of synthetic hypusine and deoxyhypusine has made it possible to develop analytical methods which allow for the measurement of these compounds in various tissues. The methods involve dansylation of extracts from the pellet remaining after perchloric acid precipitation of cell or tissue homogenates, followed by high-performance liquid chromatography. To demonstrate the utility of this approach, the impact of four polyamine analogues, N1,N11-diethylnorspermine (DENSPM), N1,N14-diethylhomospermine (DEHSPM), 1,6,12-triazadodecane [(4,5) triamine], and 1,7, 13-triazatridecane [(5,5) triamine], on hypusine levels in a human T-cell line (JURKAT) is evaluated. All four analogues are active in controlling cell growth and compete well with spermidine for the polyamine transport apparatus. After 144 h of exposure to JURKAT cells, DENSPM reduces putrescine to below detectable limits and spermidine to 10% of the level in control cells. The other three analogues diminish both putrescine and spermidine to below detectable limits. The effectiveness with which the compounds lower spermine levels is DENSPM > DEHSPM > (4,5) triamine > (5,5) triamine. The analogues decrease the activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase in a similar fashion. Of the four polyamines, DENSPM and DEHSPM are potent at lowering intracellular hypusine levels after 144 h: 59 +/- 9% and 73 +/- 12% of control levels, respectively. The other two analogues have marginal effects. |
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Authors:
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R J Bergeron; W R Weimar; R Müller; C O Zimmerman; B H McCosar; H Yao; R E Smith |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of medicinal chemistry Volume: 41 ISSN: 0022-2623 ISO Abbreviation: J. Med. Chem. Publication Date: 1998 Sep |
Date Detail:
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Created Date: 1998-10-19 Completed Date: 1998-10-19 Revised Date: 2004-11-17 |
Medline Journal Info:
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Nlm Unique ID: 9716531 Medline TA: J Med Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 3901-8 Citation Subset: IM |
Affiliation:
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Department of Medicinal Chemistry, University of Florida, Gainesville, Florida 32610-0485, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosylmethionine Decarboxylase
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antagonists & inhibitors Animals Antineoplastic Agents / analysis, metabolism, pharmacology* Biological Transport Cell Division / drug effects Chromatography, High Pressure Liquid Dansyl Compounds / chemistry Enzyme Inhibitors / analysis, metabolism, pharmacology Humans Jurkat Cells Leukemia L1210 / metabolism, pathology Lysine / analogs & derivatives*, analysis, biosynthesis, chemistry Ornithine Decarboxylase / antagonists & inhibitors Spermidine / metabolism Spermine / analogs & derivatives*, analysis, metabolism, pharmacology Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Dansyl Compounds; 0/Enzyme Inhibitors; 119422-08-1/N(1),N(14)-bis(ethyl)homospermine; 121749-39-1/N(1),N(11)-diethylnorspermine; 124-20-9/Spermidine; 34994-11-1/hypusine; 56-87-1/Lysine; 71-44-3/Spermine; 82543-85-9/deoxyhypusine; EC 4.1.1.17/Ornithine Decarboxylase; EC 4.1.1.50/Adenosylmethionine Decarboxylase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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