Linked Life Data

8669892

Source:http://linkedlifedata.com/resource/pubmed/id/8669892

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1996-8-6
pubmed:abstractText
A new class of very potent and selective non-nucleoside inhibitors of HIV reverse transcriptase (RT) has recently been identified. The prototype compound trovirdine (LY 300046 HCl) and one analogue, MSC-127, have been studied with respect to inhibition of wild-type HIV-1 RT and RT with various mutations known to give rise to resistance to other non-nucleoside RT inhibitors, namely Leu100-->Ile (Ile100), Glu138-->Arg (Arg138), Tyr181-->Cys (Cys181) and Tyr188-->His (His188). The inhibition of HIV-1 RT by trovirdine and MSC-127 was reversible and template dependent. Trovirdine inhibited HIV-1 RT with an IC50 of 0.007 microM when employing heteropolymeric primer/template (oligo-DNA/ribosomal RNA) and dGTP as substrate. Enzyme kinetic studies showed that inhibition of RT by trovirdine was non-competitive with regard to deoxynucleoside triphosphates and uncompetitive with respect to varied primer/template under steady-state conditions. The amino acid changes Leu100, Tyr181 and Tyr188 gave rise to 25-, 147- and 12-fold decrease in inhibition by trovirdine. Enzyme-kinetic studies on trovirdine have been carried out using various RT mutants and compared to the properties of the earlier reported non-nucleoside RT inhibitors 9-Cl-TIBO, nevirapine and L-697,661.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0166-3542
pubmed:author
pubmed:issnType
Print
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
331-42
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Inhibition of human immunodeficiency virus type 1 wild-type and mutant reverse transcriptases by the phenyl ethyl thiazolyl thiourea derivatives trovirdine and MSC-127.
pubmed:affiliation
Medivir AB, Huddinge, Sweden.
pubmed:publicationType
Journal Article