title: Inhibition of plasminogen activator inhibitor release in endothelial cell cultures by antisense oligodeoxyribonucleotides with a 5'-end lipophilic modification.
abstract: A series of conjugates containing residues of lipophilic alcohols covalently bound to 5' end of oligodeoxyribonucleotides targeted against human plasminogen activator inhibitor (PAI-1) mRNA was synthesized via the oxathiaphospholane approach. The highest anti-PAI-1 activity in EA.hy 926 endothelial cell cultures was found for conjugates containing menthyl or heptadecanyl groups linked with an oligonucleotide complementary to a segment of human PAI-1 mRNA. The phosphodiester antisense oligonucleotides, which otherwise exhibit only limited anti-PAI-1 activity, were found to be more active than phosphorothioate oligonucleotides when conjugated to lipophilic alcohol residues. For menthyl conjugates an evidence of antisense mechanism of inhibition was found.
authors.affiliation: Polish Academy of Sciences, Centre of Molecular and Macromolecular Studies, Department of Bioorganic Chemistry, Lódź.
authors.forename: A
authors.initials: A
authors.lastname: Kobylańska
authors.forename: E
authors.initials: E
authors.lastname: Pluskota
authors.forename: M
authors.initials: M
authors.lastname: Swiatkowska
authors.forename: M
authors.initials: M
authors.lastname: Wójcik
authors.forename: A
authors.initials: A
authors.lastname: Cierniewska-Cieślak
authors.forename: A
authors.initials: A
authors.lastname: Krakowiak
authors.forename: M
authors.initials: M
authors.lastname: Boczkowska
authors.forename: Z
authors.initials: Z
authors.lastname: Pawłowska
authors.forename: A
authors.initials: A
authors.lastname: Okruszek
authors.forename: M
authors.initials: M
authors.lastname: Koziołkiewicz
authors.forename: C S
authors.initials: CS
authors.lastname: Cierniewski
authors.forename: W J
authors.initials: WJ
authors.lastname: Stec
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D020319:Oligodeoxyribonucleotides, Antisense / Q000138:chemical synthesis / Q000235:genetics / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D017931:DNA Primers; D020319:Oligodeoxyribonucleotides, Antisense; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger