We have studied the biochemical and biological properties of 5-bromotubercidin (4-amino-5-bromo-7-beta-d-ribofuranosyl-pyrrolo [2,3-d]pyrimidine) (BrTu), a synthetic analogue of the highly cytotoxic pyrrolo[2,3-d]pyrimidine ribonucleoside antibiotic tubercidin (Tu) that interferes with numerous cellular processes, and has been shown to possess biological specificity and selectivity. Thus, BrTu entered the mammalian cell nucleotide pool by phosphorylation, was incorporated into RNA in an unmodified form and, as a consequence, reversibly inhibited (15 microM) mammalian cell growth and the synthesis of high-molecular-weight cellular RNA species (i.e., mRNA and rRNA). However, BrTu (300 microM) did not inhibit picornavirus RNA synthesis or multiplication, and thus discriminated between virus RNA-dependent and all forms of DNA-dependent RNA synthesis whether of cellular or viral origin; because of this BrTu should prove valuable as a metabolic probe for studying the cell-virus relationship. Furthermore, BrTu is a substrate for adenosine kinase (K(m)=24 microM), and is also its potent inhibitor (K(i)=0.93 microM); thus, low concentrations of BrTu (1.5 microM), which did not inhibit cell growth, blocked phosphorylation and the cellular uptake of other, highly cytotoxic pyrrolo-pyrimidine nucleoside analogues (e.g., tubercidin). This block in cellular uptake and incorporation of toxic analogues was associated with the protective effect of BrTu against cell killing by the analogues, providing a mechanism by which BrTu and these analogues can, as we reported elsewhere [J. Virol.1999, 73, 6444], be used for the selective inactivation of replicating picornaviruses.

中文翻译：

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5-溴小球菌素的生化和生物学特性：对细胞DNA定向和病毒RNA定向的RNA合成的差异作用。

我们已经研究了5-溴微球菌素（4-氨基-5-溴-7-β-d-呋喃呋喃糖基-吡咯并[2,3-d]嘧啶）（BrTu）的生物化学和生物学特性，该类似物具有高度的细胞毒性。吡咯并[2,3-d]嘧啶核糖核苷酸抗生素结核菌素（Tu）干扰许多细胞过程，并已显示具有生物学特异性和选择性。因此，BrTu通过磷酸化进入哺乳动物细胞核苷酸库，以未修饰的形式掺入RNA中，因此可逆地抑制（15 microM）哺乳动物细胞生长和高分子量细胞RNA种类（即mRNA和rRNA）。但是，BrTu（300 microM）不能抑制小核糖核酸病毒RNA的合成或繁殖，从而区分病毒RNA依赖型和DNA依赖的各种形式的RNA合成，无论是细胞来源还是病毒来源；因此，BrTu作为研究细胞与病毒关系的代谢探针应被证明是有价值的。此外，BrTu是腺苷激酶的底物（K（m）= 24 microM），也是其有效的抑制剂（K（i）= 0.93 microM）。因此，低浓度的BrTu（1.5 microM）不会抑制细胞生长，阻止了磷酸化和其他高度细胞毒性的吡咯并嘧啶核苷类似物（例如结核菌素）的细胞摄取。如我们在别处报道的[J．Virol.1999，73，6444]，