博来霉素B在利什曼原虫中的代谢及作用机制
Metabolism and mechanism of action of formycin B in Leishmania.
作者信息
Rainey P, Santi D V
出版信息
Proc Natl Acad Sci U S A. 1983 Jan;80(1):288-92. doi: 10.1073/pnas.80.1.288.
Abstract
Formycin B is a potent inhibitor of growth of the promastigote forms of Leishmania tropica, L. mexicana, L. braziliensis, and L. donovani. The metabolic products formed in these organisms are formycin B 5'-monophosphate and formycin A 5'-mono-, di-, and triphosphates, with formycin A 5'-triphosphate predominating. In addition, formycin A is extensively incorporated into RNA. From the metabolic profile, we conclude that formycin B is first converted to the 5'-monophosphate by the nucleoside phosphotransferase found in Leishmania and is subsequently converted to cytotoxic adenosine nucleotide analogs of formycin A that become incorporated into RNA. The metabolism and mechanism of formycin B appears to be qualitatively similar to that of allopurinol riboside, but quantitative differences and species selectivity suggest that these agents may have a different spectrum of activity as potential anti-leishmanial agents.
摘要
福米霉素B是热带利什曼原虫、墨西哥利什曼原虫、巴西利什曼原虫和杜氏利什曼原虫前鞭毛体生长的有效抑制剂。这些生物体中形成的代谢产物是福米霉素B 5'-单磷酸酯和福米霉素A 5'-单磷酸酯、二磷酸酯和三磷酸酯，其中福米霉素A 5'-三磷酸酯占主导。此外，福米霉素A被大量掺入RNA中。从代谢谱来看，我们得出结论，福米霉素B首先被利什曼原虫中发现的核苷磷酸转移酶转化为5'-单磷酸酯，随后转化为具有细胞毒性的福米霉素A腺苷核苷酸类似物，这些类似物会掺入RNA中。福米霉素B的代谢和作用机制在性质上似乎与别嘌呤醇核糖苷相似，但定量差异和物种选择性表明，作为潜在的抗利什曼原虫药物，这些药物可能具有不同的活性谱。
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1
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2
High-pressure liquid chromatography--ultraviolet analysis of intracellular nucleotides.高压液相色谱法——细胞内核苷酸的紫外分析
Anal Biochem. 1982 Nov 1;126(2):335-45. doi: 10.1016/0003-2697(82)90524-3.
3
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Biochem Biophys Res Commun. 1982 Sep 16;108(1):349-54. doi: 10.1016/0006-291x(82)91873-3.
4
Biological studies on formycin and formycin B.关于间型霉素和间型霉素B的生物学研究。
J Antibiot (Tokyo). 1968 Jan;21(1):5-12. doi: 10.7164/antibiotics.21.5.
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The metabolism of formycin, an adenosine analogue.阿糖腺苷类似物——间型霉素的代谢
Can J Biochem. 1969 Oct;47(10):901-8. doi: 10.1139/o69-142.
6
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Biochemistry. 1971 Apr 27;10(9):1525-31. doi: 10.1021/bi00785a003.
7
Biochemical studies of the nucleoside analogue, formycin.核苷类似物间型霉素的生化研究。
J Biol Chem. 1969 Jun 25;244(12):3243-50.
8
Studies on formycin and formycin B in cells of Ehrlich carcinoma and E. coli.关于氮杂环丙啶和氮杂环丙啶B在艾氏腹水癌细胞和大肠杆菌细胞中的研究。
J Antibiot (Tokyo). 1967 Nov;20(6):308-16.
9
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