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Nucleic Acids Research, 1989, Vol. 17, No. 1 239-252
© 1989

CHEMISTRY

Inhibition of human immunodeficiency virus (HIV-1) replication by synthetic oligo-RNA derivatives

Susumu Shibahara, Sachiko Mukai, Hirokazu Morisawa, Hideki Nakashima1, Susumu Kobayashi1 and Naoki Yamamoto1

Central Research Laboratories, Ajinomoto Co., Inc. Suzuki-cho, Kawasaki 210 1Department of Virology and Parasitology, Yamaguchi University School of Medicine 1144 Kogushi, Ube, Yamaguchi 755, Japan

Received September 2, 1988. Revised November 30, 1988. Accepted November 30, 1988.

Several synthetic 2'-0-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'-0-methyl)ribonucleoside phosphorothioates showed a potent inhibitory activity with size dependency (25-mer showed it at 1 uM), but by contrast both 2'-0-methylribo- and deoxy-oligomers with normal phosphate linkages failed to inhibit. However, it should be noted that the patched oligo(2'-0-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.


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