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dc.contributor.authorButler, Michelle Marie
dc.contributor.authorDudycz, Lech W.
dc.contributor.authorKhan, Naseema N.
dc.contributor.authorWright, George E.
dc.contributor.authorBrown, Neal C.
dc.date2022-08-11T08:08:52.000
dc.date.accessioned2022-08-23T16:10:44Z
dc.date.available2022-08-23T16:10:44Z
dc.date.issued1990-12-25
dc.date.submitted2008-08-14
dc.identifier.citation<p>Nucleic Acids Res. 1990 Dec 25;18(24):7381-7.</p>
dc.identifier.issn0305-1048 (Print)
dc.identifier.pmid2259629
dc.identifier.urihttp://hdl.handle.net/20.500.14038/33001
dc.description.abstract6-(p-Hydroxyphenylhydrazino)uracil (H2-HPUra) is a selective and potent inhibitor of the replication-specific class III DNA polymerase (pol III) of Gr+ bacteria. Although formally a pyrimidine, H2-HPUra derives its inhibitory activity from its specific capacity to mimic the purine nucleotide, dGTP. We describe the successful conversion of the H2-HPUra inhibitor prototype to a bona fide purine, using N2-(benzyl)guanine (BG) as the basis. Structure-activity relationships of BGs carrying a variety of substituents on the aryl ring identified N2-(3,4-dichlorobenzyl)guanine (DCBG) as a nucleus equivalent to H2-HPUra with respect to potency and inhibitor mechanism. DCBdGTP, the 2'-deoxyribonucleoside 5'-triphosphate form of DCBG, was synthesized and characterized with respect to its action on wild-type and mutant forms of B. subtilis DNA pol III. DCBdGTP acted on pol III by the characteristic inhibitor mechanism and formally occupied the dNTP binding site with a fit which permitted its polymerization.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2259629&dopt=Abstract ">Link to article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC332876/
dc.subjectBase Sequence; Binding Sites; DNA Polymerase III; Deoxyguanine Nucleotides; Guanine; Molecular Sequence Data; Uracil
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleDevelopment of novel inhibitor probes of DNA polymerase III based on dGTP analogs of the HPUra type: base, nucleoside and nucleotide derivatives of N2-(3,4-dichlorobenzyl)guanine
dc.typeJournal Article
dc.source.journaltitleNucleic acids research
dc.source.volume18
dc.source.issue24
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/155
dc.identifier.contextkey578119
html.description.abstract<p>6-(p-Hydroxyphenylhydrazino)uracil (H2-HPUra) is a selective and potent inhibitor of the replication-specific class III DNA polymerase (pol III) of Gr+ bacteria. Although formally a pyrimidine, H2-HPUra derives its inhibitory activity from its specific capacity to mimic the purine nucleotide, dGTP. We describe the successful conversion of the H2-HPUra inhibitor prototype to a bona fide purine, using N2-(benzyl)guanine (BG) as the basis. Structure-activity relationships of BGs carrying a variety of substituents on the aryl ring identified N2-(3,4-dichlorobenzyl)guanine (DCBG) as a nucleus equivalent to H2-HPUra with respect to potency and inhibitor mechanism. DCBdGTP, the 2'-deoxyribonucleoside 5'-triphosphate form of DCBG, was synthesized and characterized with respect to its action on wild-type and mutant forms of B. subtilis DNA pol III. DCBdGTP acted on pol III by the characteristic inhibitor mechanism and formally occupied the dNTP binding site with a fit which permitted its polymerization.</p>
dc.identifier.submissionpathgsbs_sp/155
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.source.pages7381-7


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