Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2002-4-23
pubmed:abstractText
Several groups have demonstrated that G-rich oligonucleotides forming G-quartet structures display activity as potential drugs, such as potent HIV inhibitors. The delivery of G-quartet oligonucleotides to their intracellular targets is a key obstacle to overcome for their clinical success. Here we have developed a novel system to deliver G-rich oligonucleotides into the cell nucleus, e.g., the site of HIV integration. On the basis of the property of potassium-induced formation of G-quartet structure, we explored the difference of K(+) concentrations inside (140 mM) and outside (4 mM) cells to induce the G-rich oligonucleotides to form different structures inside and outside cells. The key steps of this delivery system include the following: (i) First, the G-quartet structure is denatured to form a lipid-DNA complex, so that the molecules can be well delivered into cells. (ii) Then the delivered molecules are induced to form G-quartet structures by potassium inside cells since the G-quartet structure is the primary requirement for inhibition of HIV-1 HIV integrase (IN) activity. The molecules of a novel G-quartet HIV inhibitor, T40214, with the sequence of (GGGC)(4) were successfully delivered into the nuclei of target cells, which significantly decreased HIV-1 replication and increased the probability to target HIV-1 IN in infected cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5397-403
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11969399-Cell Line, pubmed-meshheading:11969399-DNA, pubmed-meshheading:11969399-Drug Carriers, pubmed-meshheading:11969399-Drug Delivery Systems, pubmed-meshheading:11969399-Guanine, pubmed-meshheading:11969399-HIV Integrase Inhibitors, pubmed-meshheading:11969399-HIV-1, pubmed-meshheading:11969399-Humans, pubmed-meshheading:11969399-Intracellular Fluid, pubmed-meshheading:11969399-Kinetics, pubmed-meshheading:11969399-Liposomes, pubmed-meshheading:11969399-Macromolecular Substances, pubmed-meshheading:11969399-Nucleic Acid Conformation, pubmed-meshheading:11969399-Nucleic Acid Denaturation, pubmed-meshheading:11969399-Oligodeoxyribonucleotides, pubmed-meshheading:11969399-Phosphatidylethanolamines, pubmed-meshheading:11969399-Potassium, pubmed-meshheading:11969399-Virus Integration, pubmed-meshheading:11969399-Virus Replication
pubmed:year
2002
pubmed:articleTitle
Potassium-dependent folding: a key to intracellular delivery of G-quartet oligonucleotides as HIV inhibitors.
pubmed:affiliation
Infectious Diseases Division, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA. njing@bcm.tmc.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.