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rdf:type |
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lifeskim:mentions |
umls-concept:C0012890,
umls-concept:C0018321,
umls-concept:C0028621,
umls-concept:C0028630,
umls-concept:C0057430,
umls-concept:C0178499,
umls-concept:C0182400,
umls-concept:C0205314,
umls-concept:C0243071,
umls-concept:C0243072,
umls-concept:C0332307,
umls-concept:C0679622,
umls-concept:C1527148,
umls-concept:C1527178,
umls-concept:C1705938,
umls-concept:C1999216
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pubmed:issue |
24
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pubmed:dateCreated |
1991-1-29
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/2259629-101768,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2259629-108667,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2259629-143235,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2259629-24361,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2259629-2444869,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2259629-2499883,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2259629-2515995,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2259629-3091344,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2259629-3806587,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2259629-411934,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2259629-4473549,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2259629-4628969,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2259629-4630611,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2259629-4633528,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2259629-4957971,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2259629-4992015,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2259629-6694166,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2259629-803493,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2259629-815256,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2259629-816386
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0305-1048
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
25
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7381-7
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
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pubmed:year |
1990
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pubmed:articleTitle |
Development 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.
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pubmed:affiliation |
Department of Pharmacology, University of Massachusetts Medical School, Worcester 01655.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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