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The mechanism of inhibition of human RNA polymerase by four rifamycin derivatives was investigated. Derivative AF/013 (3-formyl rifamycin SV:O-n-octyloxime) with strong hydrophobic side chains prevents the polymerase from binding to DNA and also affects the size of RNA synthesized. Derivative PR/19 (3'-acetyl-1'-benzyl-2'-methylpyrrolo[3,2-c]-4-desoxy-rifamycin SV) only affects RNA synthesis when RNA polymerase has been previously incubated with the drug or when the reaction was performed at high salt concentration [0.14 M (NH(4))(2)-SO(4)]. Our results suggest that these drugs exert their inhibitory actions by binding to the enzyme instead of DNA.

Action of Rifamycin Derivatives on RNA Polymerase of Human Leukemic Lymphocytes