Stereodependent Inhibition of Plasminogen Activator Inhibitor Type 1 by Phosphorothioate Oligonucleotides: Proof of Sequence Specificity in Cell Culture and In Vivo Rat Experiments

作者：Wojciech J. Stec, Czesław S. Cierniewski, And̀rzej Okruszek, Anna Kobylańska, Zofia Pawłowska, Maria Koziołkiewicz, Elżbieta Pluskota, Anna D. Maciaszek, Beata Rębowska, Marta Stasiak · 发表于：Antisense and Nucleic Acid Drug Development · 年份：1997 · DOI：10.1089/oli.1.1997.7.567 · 被引用次数：45 · 研究领域：Protease and Inhibitor Mechanisms、Calpain Protease Function and Regulation、Signaling Pathways in Disease

Hexadecadeoxyribonucleotides complementary to a fragment of human PAI-1 mRNA located upstream of the start codon and their phosphorothioate analogs were studied in cultured HUVECs as sequence-dependent inhibitors of PAI-1 expression. The activity of the random mixture of diastereomers of phosphorothioate hexadecanucleotide PS-16H has been compared with that of isosequential, stereoregular [All-Sp] and [All-Rp] isomers. The highest inhibitory effect on PAI-1 synthesis was observed with the [All-Sp] diastereomer. Stereorandom phosphorothioate oligonucleotide PS-16R complementary to the same region of rat PAI-1 mRNA, when injected into tail vein of rats, substantially decreased the level of PAI-1 in blood plasma.