Linked Life Data

9925303

Source:http://linkedlifedata.com/resource/pubmed/id/9925303

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1999-3-31
pubmed:abstractText
We have found that a hexadeoxyribonucleotide (5'TGGGAG3', R-95288), Koizumi, M. et al. Bioorganic & Medicinal Chemistry, 1997, 5, 2235, bearing a 3,4-dibenzyloxybenzyl (3,4-DBB) group at the 5'-end and a 2-hydroxyethylphosphate at the 3'-end, has high anti-HIV-1 activity and the least cytotoxicity in vitro and in vivo. In order to synthesize more potent hexadeoxyribonucleotides, we substituted phosphodiester (P-O) bonds in the 6-mer with the least phosphorothioate (P-S), phosphoramidate (P-N), or methylphosphonate (P-Me) bonds. When more than two P-N or P-Me bonds were introduced into a 6-mer, the phosphate-modified 6-mers had weak or no anti-HIV- activity, in spite of quadruplex structure formation. However, when P-S bonds were substituted for P-O bonds, anti-HIV-1 activity of their 6-mers did not dramatically decrease, compared with compounds substituted with P-N or P-Me bonds. The results suggest that the formation of a quadruplex structure is not always sufficient for anti-HIV-1 activity of the 6-mer, and that net negative charges derived from P-O or P-S bonds in the quadruplex are important for anti-HIV-1 activity. Moreover, among various phosphate-modified ODNs, we found that the anti-HIV-1 activity of ODN PS7 with only one P-S bond was the same as that of R-95288, both having a high stability in human plasma.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0968-0896
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2469-75
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Biologically active oligodeoxyribonucleotides. Part 11: The least phosphate-modification of quadruplex-forming hexadeoxyribonucleotide TGGGAG, bearing 3-and 5-end-modification, with anti-HIV-1 activity.
pubmed:affiliation
Exploratory Chemistry Research Lab., Sankyo Co., Ltd, Tokyo, Japan. koizum@shina.sankyo.co.jp
pubmed:publicationType
Journal Article