Kriebardis T, Meng D, Aktipis S
Biochem Biophys Res Commun. 1984 Sep 28;123(3):914-20. doi: 10.1016/s0006-291x(84)80221-1.
The inhibition of the RNA polymerase-catalyzed synthesis of RNA by daunomycin was examined. Saturation binding of daunomycin to the template leads, as expected, to complete inhibition of RNA synthesis as a result of daunomycin interference with enzyme-template interactions. However at concentrations of the inhibitor below saturation formation of the enzyme-template complex remains remarkably undisturbed, while both the transformation of this complex to an elongating complex and the elongation of the nacsent RNA chains are substantially inhibited. Clearly, daunomycin interferes with a number of different substeps of RNA synthesis and inhibits the synthesis by different mechanisms depending on the amount of inhibitor bound to the template. Elucidation of the mechanism of inhibition at low daunomycin concentrations may be a prerequisite for a better understanding of the mechanism of the pharmacological action of the drug.
研究了柔红霉素对RNA聚合酶催化的RNA合成的抑制作用。如预期的那样，柔红霉素与模板的饱和结合导致RNA合成完全抑制，这是由于柔红霉素干扰了酶-模板相互作用。然而，在抑制剂浓度低于饱和浓度时，酶-模板复合物的形成仍未受到明显干扰，而该复合物向延伸复合物的转化以及新生RNA链的延伸均受到显著抑制。显然，柔红霉素干扰了RNA合成的多个不同子步骤，并根据与模板结合的抑制剂数量通过不同机制抑制合成。阐明低浓度柔红霉素的抑制机制可能是更好地理解该药物药理作用机制的先决条件。
