Inhibitors of Bacillus subtilis DNA polymerase III. Structure-activity relations of 6-(phenylhydrazino)uracils
- 1 September 1977
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 20 (9) , 1181-1185
- https://doi.org/10.1021/jm00219a014
Abstract
6-(Phenylhydrazino)uracils inhibit the replication-specific enzyme DNA polymerase III of B. subtilis by forming a strong, reversible complex with template-primer DNA and enzyme. The phenyl ring interacts with a hydrophobic enzyme site which, on the basis of structure-activity relationships of substituted analogs, appears to possess the following characteristics: planarity or near-planarity, a finite capacity to accommodate bulky substituents and location near the domain of the enzyme active site. A mutant DNA polymerase III, derived from a mutant strain of B. subtilis selected for resistance to 6-(p-hydroxyphenylazo)pyrimidines, is resistant only to inhibitors bearing p-hydroxy or amino groups and is hypersensitive to inhibitors containing nonpolar substituents; these results suggest the existence of mutable, secondary regions of the binding site which interact with para substituents and influence the strength of the primary phenyl-enzyme interaction.This publication has 0 references indexed in Scilit: