Abstract:
:Quantitative structure-activity relationships (QSAR) of a series of 6-anilinouracil derivatives were developed for their inhibitory activity against the wild-type DNA polymerase III (pol III) and a mutant enzyme, pol III/azp-12, derived from Bacillus subtilis. Interaction between inhibitors and both enzymes appears to result solely from hydrophobic binding. Comparison of the substituent contributions indicates increased hydrophobic character and a minor change of shape of the inhibitor binding site of the mutant enzyme. Because the two enzymes have identical Km values for substrates, the inhibitor binding site is thought to be distinct from the enzyme active site.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Wright GE,Gambino JJdoi
10.1021/jm00368a013subject
Has Abstractpub_date
1984-02-01 00:00:00pages
181-5issue
2eissn
0022-2623issn
1520-4804journal_volume
27pub_type
杂志文章abstract::Increased usage of daptomycin to treat infections caused by Gram-positive bacterial pathogens has resulted in emergence of resistant mutants. In a search for more effective daptomycin analogues through medicinal chemistry studies, we found that methylation at the nonproteinogenic amino acid kynurenine in daptomycin co...
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journal_title:Journal of medicinal chemistry
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journal_title:Journal of medicinal chemistry
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