|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
11
|
|
pubmed:dateCreated |
2003-5-28
|
|
pubmed:abstractText |
We report the synthesis of a novel 2'-O-methyl (OMe) riboside phosphoramidite derivative of the G-clamp tricyclic base and incorporation into a series of small steric blocking OMe oligonucleotides targeting the apical stem-loop region of human immunodeficiency virus type 1 (HIV-1) trans- activation-responsive (TAR) RNA. Binding to TAR RNA is substantially enhanced for certain single site substitutions in the centre of the oligonucleotide, and doubly substituted anti-TAR OMe 9mers or 12mers exhibit remarkably low binding constants of <0.1 nM. G-clamp-containing oligomers achieved 50% inhibition of Tat-dependent in vitro transcription at approximately 25 nM, 4-fold lower than for a TAR 12mer OMe oligonucleotide and better than found for any other oligonucleotide tested to date. Addition of one or two OMe G-clamps did not impart cellular trans-activation inhibition activity to cellularly inactive OMe oligonucleotides. Addition of an OMe G-clamp to a 12mer OMe-locked nucleic acid chimera maintained, but did not enhance, inhibition of Tat-dependent in vitro transcription and cellular trans-activation in HeLa cells. The results demonstrate clearly that an OMe G-clamp has remarkable RNA-binding enhancement ability, but that oligonucleotide effectiveness in steric block inhibition of Tat-dependent trans-activation both in vitro and in cells is governed by factors more complex than RNA-binding strength alone.
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-10209261,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-10328810,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-10355827,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-10419493,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-10550206,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-10562489,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-10606641,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-10610767,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-10637358,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-10944537,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-10995220,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-11120883,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-11135542,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-11135550,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-11139611,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-11141056,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-11238995,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-11425312,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-11427043,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-11574678,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-11724578,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-11802733,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-11907228,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-12009901,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-12084454,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-12323396,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-12356320,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-12423089,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-12465896,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-2249668,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-7678654,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-7752225,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-8390996,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-9115264,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12771202-9920268
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-HIV Agents,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Gene Products, tat,
http://linkedlifedata.com/resource/pubmed/chemical/Oligoribonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Organophosphorus Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Viral,
http://linkedlifedata.com/resource/pubmed/chemical/Ribonucleosides,
http://linkedlifedata.com/resource/pubmed/chemical/phosphoramidite,
http://linkedlifedata.com/resource/pubmed/chemical/tat Gene Products, Human...
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jun
|
|
pubmed:issn |
1362-4962
|
|
pubmed:author |
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
1
|
|
pubmed:volume |
31
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
2759-68
|
|
pubmed:dateRevised |
2009-11-18
|
|
pubmed:meshHeading |
pubmed-meshheading:12771202-Anti-HIV Agents,
pubmed-meshheading:12771202-Base Sequence,
pubmed-meshheading:12771202-Binding Sites,
pubmed-meshheading:12771202-DNA,
pubmed-meshheading:12771202-Gene Products, tat,
pubmed-meshheading:12771202-HIV-1,
pubmed-meshheading:12771202-HeLa Cells,
pubmed-meshheading:12771202-Humans,
pubmed-meshheading:12771202-Methylation,
pubmed-meshheading:12771202-Oligoribonucleotides,
pubmed-meshheading:12771202-Organophosphorus Compounds,
pubmed-meshheading:12771202-RNA, Viral,
pubmed-meshheading:12771202-Ribonucleosides,
pubmed-meshheading:12771202-Transcriptional Activation,
pubmed-meshheading:12771202-tat Gene Products, Human Immunodeficiency Virus
|
|
pubmed:year |
2003
|
|
pubmed:articleTitle |
Steric inhibition of human immunodeficiency virus type-1 Tat-dependent trans-activation in vitro and in cells by oligonucleotides containing 2'-O-methyl G-clamp ribonucleoside analogues.
|
|
pubmed:affiliation |
Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
|
|
pubmed:publicationType |
Journal Article
|
