Hydralazine inhibition of the post-translational hydroxylation of deoxyhypusine, a polyamine-derived amino acid.

Hydralazine inhibition of the post-translational hydroxylation of deoxyhypusine, a polyamine-derived amino acid.
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肼屈嗪抑制脱氧马尿碱(一种多胺衍生氨基酸)的翻译后羟基化。

DOI:
10.1016/0006-2952(84)90462-3
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发表时间:
1984
影响因子:
5.8
通讯作者:
P. Gallop
P. Gallop
中科院分区:
医学2区
文献类型:
--
作者:
M. Paz;B. M. Torrelio;P. Gallop

文献摘要

被引文献

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对数生长的中国仓鼠卵巢细胞在 [1, 4-14C] 腐胺存在下培养,合成一种含有不常见氨基酸马尿嘧啶 [Nε-(4-氨基-2-羟丁基)赖氨酸] 的蛋白质。通过二维凝胶电泳和荧光成像技术分离并鉴定了该蛋白质。通过离子交换色谱法从细胞蛋白的酸水解产物中分离出标记的马尿苷,通过氧化降解和产物分析来鉴定。肼屈嗪是治疗中度至重度高血压最常用的药物之一,添加到培养物中会导致含有前体氨基酸脱氧马尿苷 [Nε-(4-氨基丁基)赖氨酸] 的蛋白质积累。该中间体及其随后转化为hypusine的证明表明,合成分几个步骤进行,其中一个涉及羟基化反应,该反应可以被肼屈嗪抑制。
Logarithmically growing Chinese hamster ovary cells, cultured in the presence of [1, 4-14C] putrescine, synthesize a protein(s) containing the unusual amino acid hypusine [Nε-(4-amino-2-hydroxybutyl)lysine]. This protein was separated and identified by two-dimensional gel electrophoresis and fluorography. The labeled hypusine isolated from an acid hydrolysate of the cell protein by ion exchange chromatography was identified by oxidative degradation and analyses of the products. Hydralazine, one of the most frequently prescribed drugs for the treatment of moderate to severe hypertension, added to the culture, resulted in the accumulation of a protein(s) containing the precursor amino acid deoxyhypusine [Nε-(4-aminobutyl)lysine]. Demonstration of this intermediate and its subsequent conversion to hypusine suggests that the synthesis occurs in several steps, one of these involving a hydroxylation reaction which can be inhibited by hydralazine.