Selective repression of transcription by base sequence specific synthetic polymers.
We report the effect of novel synthetic polymers on deoxyribonucleic acid (DNA) directed ribonucleic acid (RNA) synthesis in vitro. Polymers contained base-selective monomers, including a GC-specific phenazine derivative and an AT-specific triphenylmethane dye. Radical chain polymerization was carried out in aqueous solution by using monomers bound to a template DNA, which was obtained from either lambda or T7 bacteriophage. Polymers were isolated and reannealed with DNA samples, including competitive mixtures of T7 and lambda DNAs. We measured transcription from DNA-polymer complexes by using Escherichia coli RNA polymerase and determined not only the reduction in total transcription levels but also the relative inhibition of lambda- or T7-specific transcription by using a hybridization assay. The results show that micromolar concentrations of individual dyes are sufficient to cause substantial inhibition of transcription when the dyes are incorporated into polymers. More significantly, a number of the polymers inhibited more strongly transcription from the DNA which had served as template for polymer synthesis than from the DNA present as competitor in the annealing process. We conclude that template synthesis of DNA-binding polymers can lead to preferential inhibition of function of the original template. The apparent relative affinity of polymer for competing DNAs can be altered by at least an order of magnitude depending on which DNA was used as the synthesis template. The results offer a new approach to improving the specificity of DNA-binding drugs.
D004396:Coloring Agents / Q000494:pharmacology*; D004279:DNA, Viral; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology*; D007700:Kinetics; D008433:Mathematics; D011108:Polymers / Q000494:pharmacology*; D013053:Spectrophotometry; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects*
D004396:Coloring Agents; D004279:DNA, Viral; D011108:Polymers; D012321:DNA-Directed RNA Polymerases