Open AccessInhibition of plasminogen activator inhibitor release in endothelial cell cultures by antisense oligodeoxyribonucleotides with a 5'-end lipophilic modification.
Author(s) -
Anna Kobylańska,
Elżbieta Pluskota,
Maria Świątkowska,
Marzena Wójcik,
Aleksandra Cierniewska-Cieślak,
Agnieszka Krakowiak,
Małgorzata Boczkowska,
Zofia Pawłowska,
And̀rzej Okruszek,
Maria Koziołkiewicz,
Czesław S. Cierniewski,
Wojciech J. Stec
Publication year - 1999
Publication title -
acta biochimica polonica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.452
H-Index - 78
eISSN - 1734-154X
pISSN - 0001-527X
DOI - 10.18388/abp.1999_4140
Subject(s) - phosphodiester bond , chemistry , oligonucleotide , plasminogen activator , conjugate , biochemistry , tissue plasminogen activator , plasminogen activator inhibitor 1 , activator (genetics) , covalent bond , enzyme , endothelial stem cell , stereochemistry , microbiology and biotechnology , in vitro , biology , rna , receptor , dna , gene , mathematical analysis , mathematics , organic chemistry , endocrinology
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.