Abstract：
:Resolvase enzymes that cleave DNA four-way (Holliday) junctions are required for poxvirus replication, but clinically useful inhibitors have not been developed. Here, we report an assay for resolvase cleavage activity based on fluorescence polarization (FP) for high-throughput screening and mechanistic studies. Initial analysis showed that cleavage of a fluorescently labeled Holliday junction substrate did not yield an appreciable change in FP, probably because the cleavage product did not have sufficiently increased mobility to yield a strong FP signal. Iterative optimization yielded a substrate with an off-center DNA bulge, which after cleavage released a labeled short stand and yielded a greatly reduced FP signal. Using this assay, 133,000 compounds were screened, identifying 1-hydroxy-1,8-naphthyridin-2(1H)-one compounds as inhibitors. Structure-activity studies revealed functional parallels to Food and Drug Administration (FDA)-approved drugs targeting the related human immunodeficiency virus integrase enzyme. Some 1-hydroxy-1,8-naphthyridin-2(1H)-one compounds showed anti-poxvirus activity.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Culyba M,Hwang Y,Attar S,Madrid PB,Bupp J,Huryn D,Sanchez L,Grobler J,Miller MD,Bushman FDdoi
10.1093/nar/gks325subject
Has Abstractpub_date
2012-09-01 00:00:00pages
e124issue
16eissn
0305-1048issn
1362-4962pii
gks325journal_volume
40pub_type
杂志文章abstract：:Calf lens messenger fractions have been purified on poly(dT)-cellulose. The purified RNA's have been analyzed as nucleosides by a method which can be used on a micro-scale with highly reproduceble results. Both the 10S and 14S lens mRNA contain poly A sequences. The poly A content found in 14S mRNA cannot account for ...
journal_title：Nucleic acids research
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doi：10.1093/nar/1.2.245
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abstract：:Several plasmids which direct the expression of human interferon-gamma (IFN-gamma) cDNA in the yeast Saccharomyces cerevisiae under the transcriptional control of the 3-phosphoglycerate kinase (PGK) promoter have been constructed. Up to 25 x 10(6) units per liter culture of biologically active IFN-gamma are synthesize...
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journal_title：Nucleic acids research
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journal_title：Nucleic acids research
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journal_title：Nucleic acids research
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journal_title：Nucleic acids research
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更新日期：2003-06-15 00:00:00
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journal_title：Nucleic acids research
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journal_title：Nucleic acids research
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