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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2010-2-25
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pubmed:abstractText |
Binding of hepatitis C virus (HCV) RNA to core, the capsid protein, results in the formation of the nucleocapsid, the first step in the assembly of the viral particle. A novel assay was developed to discover small molecule inhibitors of core dimerization. This assay is based on time-resolved fluorescence resonance energy transfer (TR-FRET) between anti-tag antibodies labeled with either europium cryptate (Eu) or allophycocyanin (XL-665). The N-terminal 106-residue portion of core protein (core106) was tagged with either glutathione-S-transferase (GST) or a Flag peptide. Tag-free core106 was selected as the reference inhibitor. The assay was used to screen the library of pharmacologically active compounds (LOPAC) consisting of 1,280 compounds and a 2,240-compound library from the Center for Chemical Methodology and Library Development at Boston University (CMLD-BU). Ten of the 28 hits from the primary TR-FRET run were confirmed in a secondary amplified luminescent proximity homogeneous assay (ALPHA screen). One hit was further characterized by dose-response analysis yielding an IC(50) of 9.3 microM. This 513 Da compound was shown to inhibit HCV production in cultured hepatoma cells.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20035614-10718937,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20035614-12097189,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20035614-12655344,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20035614-12844435,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20035614-15220408,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20035614-15939869,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20035614-15947137,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20035614-15951748,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20035614-15957938,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20035614-16050712,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20035614-16153061,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20035614-17302247,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20035614-17449128,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20035614-17537845,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20035614-17704692,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20035614-18075579,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20035614-18369478,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20035614-18517255,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20035614-19264632,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20035614-2523562,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20035614-9385865
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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 |
Feb
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pubmed:issn |
1557-8127
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
8
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
96-105
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pubmed:dateRevised |
2011-7-22
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pubmed:meshHeading |
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pubmed:year |
2010
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pubmed:articleTitle |
A time-resolved fluorescence-resonance energy transfer assay for identifying inhibitors of hepatitis C virus core dimerization.
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pubmed:affiliation |
Department of Infectology, The Scripps Research Institute-Scripps Florida, Jupiter, Florida 33458, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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