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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.
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p.679-691,fig.
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- Polish Academy of Sciences, H.Sienkiewicza 112, 90-363 Lodz, Poland
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Bibliografia
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Bibliografia
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bwmeta1.element.agro-article-cb4eacd7-c98d-47a8-8ddc-f3d971910203