title: Studies on the mode of action of partially thiolated polycytidylic acid (MPC), a novel type of antineoplastic agent.
abstract: Partially thiolated polycytidylic acid (MPC), a representative member of the "antitemplate" class of novel chemotherapeutic agents, is a potent inhibitor of the E. coli DNA-dependent RNA polymerase. It inhibited 50% of the enzymic reaction at a concentration of 6 micrometers. Kinetic studies indicated that MPC had no effect on the chain elongation of the transcription process, but it appeared to inhibit the initiation of RNA synthtesis presumably by competing with the DNA template for binding to the RNA polymerase. Binding studies, using a gel filtration method, showed that MPC and the RNA polymerase formed a stable complex which was not dissociated by 0.3 M NaCl. It is inferred that mixed disulfide linkage(s) might have been formed between the enzyme and MPC. The implications of these findings are discussed.
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors; D004926:Escherichia coli / Q000201:enzymology; D007700:Kinetics; D011066:Poly C / Q000494:pharmacology*; D011131:Polyribonucleotides / Q000494:pharmacology*; D012293:Rifampin / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D011131:Polyribonucleotides; D011066:Poly C; D012321:DNA-Directed RNA Polymerases; D012293:Rifampin