Inhibition of plasminogen activator inhibitor release in endothelial cell cultures by antisense oligodeoxyribonucleotides with a 5'-end lipophilic modification.

A Kobylańska; E Pluskota; M Swiatkowska; M Wójcik; A Cierniewska-Cieślak; A Krakowiak; M Boczkowska; Z Pawłowska; A Okruszek; M Koziołkiewicz; C S Cierniewski; W J Stec

doi:10.18388/abp.1999_4140

Inhibition of plasminogen activator inhibitor release in endothelial cell cultures by antisense oligodeoxyribonucleotides with a 5'-end lipophilic modification.

A Kobylańska Polish Academy of Sciences, Centre of Molecular and Macromolecular Studies, Department of Bioorganic Chemistry, Lódź.;
E Pluskota
M Swiatkowska
M Wójcik
A Cierniewska-Cieślak
A Krakowiak
M Boczkowska
Z Pawłowska
A Okruszek
M Koziołkiewicz
C S Cierniewski
W J Stec

DOI: https://doi.org/10.18388/abp.1999_4140

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.

Published

1999-09-30

Issue

Vol. 46 No. 3 (1999)

Section

Articles

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