Inhibition of Bacillus subtilis DNA polymerase III by arylhydrazinopyrimidines. Novel properties of 2-thiouracil derivatives.
6-(p-Tolylhydrazino)-uracil, 6-(p-tolylhydrazino)-isocytosine and 6-(p-tolylhydrazino)-2-thiouracil were synthesized and compared with respect to their chemical properties, their activity as inhibitors of DNA polymerase III of  Bacillus subtilis, and their capacity to induce the formation of a complex between polymerase III and template DNA. As expected from earlier studies of analogous hydroxyphenylhydrazino compounds, the effects of the uracil derivative were reversed specifically by dGTP and those of the isocytosine derivative were reversed specifically by dATP. In contrast, reversal of the effects of the thiouracil derivative required both dGTP and dATP. The unique capacity of the 2-thiouracil analog to mimic either purine deoxyribonucleotide appears to reside in its ability to undergo tautomerism between the 2-thione and 2-thiol forms, which can pair with, respectively, template cytosine and thymine.
D001412:Bacillus subtilis / Q000187:drug effects / Q000201:enzymology*; D004254:DNA Nucleotidyltransferases / Q000037:antagonists & inhibitors*; D006834:Hydrazines / Q000494:pharmacology*; D007536:Isomerism; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013889:Thiouracil / Q000494:pharmacology*
D006834:Hydrazines; D013889:Thiouracil; D004254:DNA Nucleotidyltransferases