Inhibitors of Bacillus subtilis DNA polymerase III. 6-(Arylalkylamino)uracils and 6-anilinouracils

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Abstract
6-(Benzylamino)uracils and substituted 6-anilinouracils apparently are potent inhibitors of B. subtilis DNA polymerase III with a mechanism identical with that of 6-(phenylhydrazino)uracils. Higher phenylalkylamino homologs are progressively weaker inhibitors of the enzyme. Examination of effects of substituents on activity of 6-(benzylamino)uracils against wild-type and mutant enzymes and preliminary results for 6-anilinouracils have permitted further dissection of the mechanism of inhibition. Experimental results indicate that the polymerase inhibitor binding site is compact, accommodating only small alterations in the distance between the uracil and phenyl rings, that the phenyl ring, which provides the major contribution to inhibitor-enzyme binding, adopts a specific active conformation and an enzyme site which interacts with substituents in the phenyl ring forms a part of the active site of DNA polymerase III.