Inhibition of herpes simplex virus 1 reproduction with hydrophobized antisense oligonucleotides.
Antisense oligonucleotides were modified by their ends with hydrophobic substituents which permitted enhancing their activity. The effect of hydrophobized oligonucleotides on reproduction of Herpes Simplex Virus type 1 in Vero cells was studied. Two types of oligonucleotides were used: a 12-mer complementary to the splicing site 983-994 of early mRNA-5 of the virus and 19-mer complementary to the site of mRNA that encodes the virus DNA-polymerase. These oligonucleotides were modified by 5'-ends with n-undecyl or cholesteryl moieties and by 3'-ends with acridine or 1,7-heptanediol. In comparison with the unmodified oligonucleotides the hydrophobized ones were significantly more active and inhibited HSV-1 infection at micromolar concentrations.
Vinogradov
S V
SV
Moscow Institute of Biotechnology Inc., Russia.
Suzdaltseva
Y
Y
Alakhov VYu
Kabanov
A V
AV
D000166:Acridines / Q000737:chemistry; D000818:Animals; D001483:Base Sequence; D002784:Cholesterol / Q000737:chemistry; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D006018:Glycols / Q000737:chemistry; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development*; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000494:pharmacology*; D012326:RNA Splicing; D012333:RNA, Messenger; D012367:RNA, Viral; D014709:Vero Cells
D000166:Acridines; D006018:Glycols; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D012367:RNA, Viral; C007927:1,7-heptanediol; D002784:Cholesterol; D004259:DNA-Directed DNA Polymerase