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
Polish Academy of Sciences, Centre of Molecular and Macromolecular Studies, Department of Bioorganic Chemistry, Lódź.
Acta Biochim Pol. 1999;46(3):679-91.
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.
通过氧硫磷杂环戊烷方法合成了一系列缀合物，这些缀合物含有与靶向人纤溶酶原激活物抑制剂（PAI-1）mRNA的寡脱氧核糖核苷酸5'端共价结合的亲脂性醇残基。在EA.hy 926内皮细胞培养物中，发现含有与人类PAI-1 mRNA片段互补的寡核苷酸连接的薄荷基或十七烷基的缀合物具有最高的抗PAI-1活性。当与亲脂性醇残基缀合时，原本仅表现出有限抗PAI-1活性的磷酸二酯反义寡核苷酸比硫代磷酸酯寡核苷酸更具活性。对于薄荷基缀合物，发现了抑制的反义机制的证据。
