Linked Life Data

12207905

Source:http://linkedlifedata.com/resource/pubmed/id/12207905

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2002-9-4
pubmed:abstractText
The crucial functions of HIV-1 nucleocapsid-p7 protein (NC-p7) at different stages of HIV replication are dependent on its nucleic acid binding properties. In this study, a search has been made to identify antagonists of the interaction between NC-p7 and d(TG)(4). A chemical library of approximately 2000 small molecules (the NCI Diversity Set) was screened, of the 26 active inhibitors that were identified, five contained a xanthenyl ring structure. Further analysis of 63 structurally related compounds led to the identification of 2,3,4,5-tetrachloro-6-(4('),5('),6(')-trihydroxy-3(')-oxo-3H-xanthen-9(')-yl)benzoic acid, which binds to NC-p7 stoichiometrically. This compound exerted a significant anti-HIV activity in vitro with an IC(50) of 16.6+/-4.3 microM (means+/-SD). Synthetic variants lacking the two hydroxyls at positions 4(') and 5(') in the xanthenyl ring system failed to bind NC-p7 and showed significantly less protection against HIV infection. Molecular modeling predicts that these hydroxyl groups would bind to the amide nitrogen of Gly(35) with other contacts at the carbonyl oxygens of Gly(40) and Lys(33).
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0006-291X
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
296
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1228-37
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Identification of HIV-1 nucleocapsid protein: nucleic acid antagonists with cellular anti-HIV activity.
pubmed:affiliation
Protein Chemistry Laboratory, SAIC-Frederick, Inc., NCI Frederick, 21702, Frederick, MD, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.