5′-Linked lipid-oligodeoxyribonucleotide derivatives as inhibitors of human immunodeficiency virus replication

✍ Scribed by Sang-Gug Kim; Hideki Nakashima; Yoko Shoji; Takabumi Inagawa; Naoki Yamamoto; Yasuhiro Kinzuka; Kazuyuki Takai; Hiroshi Takaku

• Book ID: 103992274
• Publisher: Elsevier Science
• Year: 1996
• Tongue: English
• Weight: 633 KB
• Volume: 4
• Category: Article
• ISSN: 0968-0896
• DOI: 10.1016/0968-0896(96)00043-0

✦ Synopsis

The covalent attachment of a phospholipid moiety, bound to the 5'-ends of phosphodiester and phosphorothioate oligonucleotides (L-ODNs and LS-ODNs), was achieved using H-phosphonate chemistry, and the lipid-oligonucleotides were assayed for the inhibition of virus replication in HIV-1 infected MT-4 cells. In the anti-HIV activity test, lipid-phosphorothioate oligonucleotides showed higher anti-HIV activities than non-lipid-phosphorothioate oligonucleotides, at the low concentration of 0.04 microM. LS-ODNs can inhibit HIV-1 reverse transcriptase activity through interactions with the enzyme. We found that the covalent attachment of a phospholipid group to the 5'-end of the phosphorothioate oligonucleotide enhances its nonsequence specific anti-HIV activity.