Stereodependent inhibition of plasminogen activator inhibitor type 1 by phosphorothioate oligonucleotides: proof of sequence specificity in cell culture and in vivo rat experiments.
Antisense Nucleic Acid Drug Dev
; 7(6): 567-73, 1997 Dec.
Article
em En
| MEDLINE
| ID: mdl-9450914
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tionucleotídeos
/
Endotélio Vascular
/
Inibidor 1 de Ativador de Plasminogênio
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Antisense Nucleic Acid Drug Dev
Assunto da revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
FARMACOLOGIA
Ano de publicação:
1997
Tipo de documento:
Article