Abstract
Several synthetic 2'-O-methyl-RNA oligomers and their derivatives have been evaluated for inhibitory effect against HIV-induced cytopathic effect and expression of the virus specific antigen in cultured MT-4 cells. In this study, oligo(2'-O-methyl)ribonucleoside phosphorothioates showed a potent inhibitory activity with size dependency (25-mer showed it at 1 microM), but by contrast both 2'-O-methylribo- and deoxy-oligomers with normal phosphate linkages failed to inhibit. However, it should be noted that the patched oligo(2'-O-methyl)ribonucleotide (20-mer), in which five linkages at 5'- and three linkages at 3'-ends of normal phosphates were replaced with thiophosphates, has recovered the substantial inhibitory effect. These results show that the size of oligomer and phosphorothioate linkages, probably resistant to exolytic nucleases, are essential for exhibiting antiviral activity.
MeSH Terms
Base Sequence
Cell Line
Genes, Viral
HIV-1/drug effects,genetics,physiology
Humans
Molecular Sequence Data
Oligonucleotides/pharmacology
Virus Replication/drug effects
Chemicals
Oligonucleotides
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Shibahara S
Central Research Laboratories, Ajinomoto Co., Inc., Kawasaki, Japan.
Mukai S
Morisawa H
Nakashima H
Kobayashi S
Yamamoto N
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