Linked Life Data

9561202

Source:http://linkedlifedata.com/resource/pubmed/id/9561202

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1998-6-8
pubmed:abstractText
VX-478 (141W94), a potent inhibitor of HIV protease, is in late stage clinical trials for the treatment of HIV infection and AIDS. Resistant viruses were raised in vitro by passage of HIV-1IIIB in the presence of increasing concentrations of VX-478 and the related hydroxyethylamino sulfonamide inhibitor VB-11,328. By direct PCR analysis of selected viruses, a number of mutations were identified (L10F, M46I, I47V, I50V and I84V) in the protease gene. These mutations were introduced into recombinant HIV-1 protease and the mutant enzymes assayed against a panel of inhibitors of diverse chemical structure. For VX-478, significant increases in IC90 and Ki were observed for virus or protease, respectively, containing I50V single mutation or an M46I/I47V/I50V triple mutation. The mutant proteases were also characterized for their kinetic competence to process substrates representing cleavage sites of gag-pol viral polypeptide. The kinetic data were interpreted with the aid of molecular modeling to understand the effect of mutations on inhibitor binding and processing of the gag-pol polypeptide to generate infective virions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0065-2598
pubmed:author
pubmed:issnType
Print
pubmed:volume
436
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
75-83
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
In vitro selection and characterization of VX-478 resistant HIV-1 variants.
pubmed:affiliation
Vertex Pharmaceuticals Incorporated, Cambridge, Massachusetts 02139, USA.
pubmed:publicationType
Journal Article, Review