PT  - JOURNAL ARTICLE
AU  - JOSEPH W. CRANSTON
AU  - RAYMOND W. RUDDON
TI  - The Inhibition of Ribonucleic Acid Polymerase from <em>Escherichia coli</em> by 6-Chloro-8-aza-9-cyclopentylpurine
DP  - 1973 Jan 01
TA  - Molecular Pharmacology
PG  - 81--92
VI  - 9
IP  - 1
4099  - http://molpharm.aspetjournals.org/content/9/1/81.short
4100  - http://molpharm.aspetjournals.org/content/9/1/81.full
SO  - Mol Pharmacol1973 Jan 01; 9
AB  - The inhibition of RNA synthesis in vitro by the purine nucleoside analogue 6-chloro-8-aza-9-cyclopentylpurine has been characterized. This compound was found to be a noncompetitive inhibitor of the incorporation of nucleoside triphosphates into RNA by binding to DNA-dependent RNA polymerase (ribonucleoside triphosphate:RNA nucleotidyltransferase, EC 2.7.7.6) isolated from Escherichia coil. The DNA-binding and initiation functions of the enzyme were blocked, but the compound did not affect RNA chain elongation. Studies of the interactions of 6-chloro-8-aza-9-cyclopentylpurine with amino acids, N-acetylamino acid analogues, and β-mercaptoethanol indicated that the drug reacts primarily with sulfhydryl groups of RNA polymerase. The inhibition could be partially reversed by dithiothreitol. The data suggest that 6-chloro-8-aza-9-cyclopentylpurine acts by inhibiting RNA polymerase function in a manner similar to the reversible sulfhydryl inhibitor p-chloromercuribenzoate. ACKNOWLEDGMENT The authors wish to thank Mrs. Donna Lundeen for her help in the preparation of the manuscript.