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1 Acta Biochimica Polonica

1 1999

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

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Kobylanska A. , Pluskota E. , Swiatkowska M. , Wojcik M. , Cierniewska-Cieslak A. , Krakowiak A. , Boczkowska M. , Pawlowska Z. , Okruszek A. , Koziolkiewicz M. , Cierniewski C. S. , Stec W. J.

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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.