文章基本信息

标题：Formation of Spermidine or Norspermidine from Synthetic Diacetylpolyamines by Acetylpolyamine Oxidase in Cultured Cells
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作者：Koichi Takao ; Tomohiro Ozawa ; Satoko Shibata 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2007
卷号：30
期号：12
页码：2389-2393
DOI：10.1248/bpb.30.2389
出版社：The Pharmaceutical Society of Japan
摘要：Prodrugs that can readily release polyamine into cells without the problem of generating cytotoxic compound by serum amine oxidase would be extremely useful for elucidation of polyamine function. As linear polyamines with acetamide groups on both sides are thought to be stable in the presence of serum amine oxidase and produce polyamines by the catalytic reaction of acetylpolyamine oxidase (PAO), a series of diacetyltetraamines, diacetylpentaamines and diacetylhexaamines was prepared as prodrugs and tested for substrate activity against PAO, partially purified from rat liver. Of the compounds, N ¹, N ¹⁵-diacetyl-1,15-diamino-4,8,12-triazapentadecane (DA3333) and N ¹, N ¹⁶-diacetyl-1,16-diamino-4,8,13-triazahexadecane (DA3343) were found to be stable in culture medium containing newborn bovine serum, and to produce reasonable amounts of norspermidine and spermidine, respectively. DA3333 and DA3343 were then applied to 1-aminooxy-3-aminopropane (AOAP)-treated HTC cells with depleted putrescine and spermidine, and arrested growth. Cell growth recovered with DA3333 and DA3343, but growth rate was reduced in cells with added DA3333 compared with growth rates in cells with added DA3343 and control cells untreated with AOAP. Significant amounts of norspermidine and spermidine were found in cells with added DA3333 and DA3343, respectively. These results show the potential use of diacetylpolyamines in introducing polyamines into cells.
关键词：polyamine;acetylpolyamine oxidase;diacetylpolyamine;acetylpolyamine;HTC cell;cell culture