Lesiak K, Torrence P F
J Med Chem. 1986 Jun;29(6):1015-22. doi: 10.1021/jm00156a020.
The 8-bromoadenosine analogue of 5'-O-triphosphoadenylyl(2'----5')adenylyl(2'----5')adenosine (2-5A) and its derivatives were synthesized, and their biological activity was evaluated in mouse L cell extracts. All compounds, except 5'-dephosphorylated "cores" bound to the 2-5A-dependent endonuclease with a relative activity, depending on the derivative, of 1 to 0.035 of that of 2-5A trimer. 8-Bromoadenylate trimer 5'-mono-, -di, and -triphosphates inhibited protein synthesis with a relative activity of 0.0023, 0.050, and 0.015 compared to 2-5A. Tetramer 5'-monophosphate also inhibited protein synthesis (relative activity 0.0033). The corresponding pentamer 5'-monophosphate did not; however, the pentamer 5'-diphosphate was able to inhibit translation (relative activity 0.0092). All compounds that possessed inhibitory activity in the protein synthesis inhibition assay gave ribosomal RNA cleavage patterns characteristic of the action of 2-5A-dependent endonuclease. Thus, 8-bromination of the all of the adenine rings of 2-5A leads to 20- to 70-fold reduction in the biological activity of the corresponding 5'-di- and -triphosphate, respectively; however, this same alteration of the three adenine moieties gives rise to a 5'-monophosphate with much enhanced translational inhibitory activity compared to the parent 2-5A trimer 5'-monophosphate.
5'-O-三磷酸腺苷酰基(2'→5')腺苷酰基(2'→5')腺苷(2-5A)的8-溴腺苷类似物及其衍生物被合成出来，并在小鼠L细胞提取物中评估了它们的生物活性。除了与2-5A依赖性核酸内切酶结合的5'-去磷酸化“核心”外，所有化合物的相对活性取决于衍生物，为2-5A三聚体活性的1至0.035。8-溴腺苷酸三聚体的5'-单磷酸、-二磷酸和-三磷酸抑制蛋白质合成，与2-5A相比，相对活性分别为0.0023、0.050和0.015。四聚体5'-单磷酸也抑制蛋白质合成(相对活性0.0033)。相应的五聚体5'-单磷酸则不然；然而，五聚体5'-二磷酸能够抑制翻译(相对活性0.0092)。在蛋白质合成抑制试验中具有抑制活性的所有化合物都给出了2-5A依赖性核酸内切酶作用特有的核糖体RNA切割模式。因此，2-5A所有腺嘌呤环的8-溴化分别导致相应的5'-二磷酸和-三磷酸的生物活性降低20至70倍；然而，与母体2-5A三聚体5'-单磷酸相比，三个腺嘌呤部分的这种相同改变产生了具有大大增强的翻译抑制活性的5'-单磷酸。
