Inhibition of plasminogen activator inhibitor release in endothelial cell cultures by antisense oligodeoxyribonucleotides with a 5'-end lipophilic modification
Kobylańska, A.; Pluskota, E.; Swiatkowska, M.; Wójcik, M.; Cierniewska-Cieślak, A.; Krakowiak, A.; Boczkowska, M.; Pawłowska, Z.; Okruszek, A.; Koziołkiewicz, M.; Cierniewski, C.S.; Stec, W.J.
Acta Biochimica Polonica 46(3): 679-691
1999
ISSN/ISBN: 0001-527X PMID: 10698276 Document Number: 504761
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.