|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0004083,
umls-concept:C0019704,
umls-concept:C0021469,
umls-concept:C0056695,
umls-concept:C0086418,
umls-concept:C0961954,
umls-concept:C1100939,
umls-concept:C1167622,
umls-concept:C1328819,
umls-concept:C1333336,
umls-concept:C1521761,
umls-concept:C2698650
|
|
pubmed:issue |
10
|
|
pubmed:dateCreated |
2007-5-10
|
|
pubmed:abstractText |
Human immunodeficiency virus 1 (HIV-1) trans-activator Tat recruits the human transcriptional coactivator PCAF (p300/CREB binding protein-associated factor) to facilitate transcription of the integrated HIV-1 provirus. We report here structure-based lead optimization of small-molecule inhibitors that block selectively Tat and PCAF association in cells. Our lead optimization was guided by grand-canonical ensemble simulation of the receptor/lead complex that leads to definition of chemical modifications with improved lead affinity through displacing weakly bound water molecules at the ligand-receptor interface.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Gene Products, tat,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Acetyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Propylamines,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Water,
http://linkedlifedata.com/resource/pubmed/chemical/p300-CBP Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/p300-CBP-associated factor,
http://linkedlifedata.com/resource/pubmed/chemical/tat Gene Products, Human...
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
May
|
|
pubmed:issn |
0022-2623
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
17
|
|
pubmed:volume |
50
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
2285-8
|
|
pubmed:dateRevised |
2008-11-21
|
|
pubmed:meshHeading |
pubmed-meshheading:17444627-Cell Cycle Proteins,
pubmed-meshheading:17444627-Gene Products, tat,
pubmed-meshheading:17444627-Genes, Reporter,
pubmed-meshheading:17444627-HIV Long Terminal Repeat,
pubmed-meshheading:17444627-HIV-1,
pubmed-meshheading:17444627-Histone Acetyltransferases,
pubmed-meshheading:17444627-Humans,
pubmed-meshheading:17444627-Ligands,
pubmed-meshheading:17444627-Luciferases,
pubmed-meshheading:17444627-Models, Molecular,
pubmed-meshheading:17444627-Monte Carlo Method,
pubmed-meshheading:17444627-Promoter Regions, Genetic,
pubmed-meshheading:17444627-Propylamines,
pubmed-meshheading:17444627-Protein Structure, Tertiary,
pubmed-meshheading:17444627-Transcription, Genetic,
pubmed-meshheading:17444627-Transcription Factors,
pubmed-meshheading:17444627-Water,
pubmed-meshheading:17444627-p300-CBP Transcription Factors,
pubmed-meshheading:17444627-tat Gene Products, Human Immunodeficiency Virus
|
|
pubmed:year |
2007
|
|
pubmed:articleTitle |
Structure-guided optimization of small molecules inhibiting human immunodeficiency virus 1 Tat association with the human coactivator p300/CREB binding protein-associated factor.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|
