Inhibition of plasminogen activator inhibitor release in endothelial cell cultures by antisense oligodeoxyribonucleotides with a 5'-end lipophilic modification.
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.
Kobylańska
A
A
Polish Academy of Sciences, Centre of Molecular and Macromolecular Studies, Department of Bioorganic Chemistry, Lódź.
Pluskota
E
E
Swiatkowska
M
M
Wójcik
M
M
Cierniewska-Cieślak
A
A
Krakowiak
A
A
Boczkowska
M
M
Pawłowska
Z
Z
Okruszek
A
A
Koziołkiewicz
M
M
Cierniewski
C S
CS
Stec
W J
WJ
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
D017931:DNA Primers; D020319:Oligodeoxyribonucleotides, Antisense; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger