Kim S G, Nakashima H, Shoji Y, Inagawa T, Yamamoto N, Kinzuka Y, Takai K, Takaku H
Department of Industrial Chemistry, Chiba Institute of Technology, Japan.
Bioorg Med Chem. 1996 Apr;4(4):603-8. doi: 10.1016/0968-0896(96)00043-0.
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.
利用H-膦酸酯化学方法实现了磷脂部分与磷酸二酯和硫代磷酸酯寡核苷酸（L-ODN和LS-ODN）5'-末端的共价连接，并检测了脂质寡核苷酸对HIV-1感染的MT-4细胞中病毒复制的抑制作用。在抗HIV活性测试中，在低浓度0.04 microM时，脂质硫代磷酸酯寡核苷酸显示出比非脂质硫代磷酸酯寡核苷酸更高的抗HIV活性。LS-ODN可通过与该酶相互作用抑制HIV-1逆转录酶活性。我们发现，将磷脂基团共价连接到硫代磷酸酯寡核苷酸的5'-末端可增强其非序列特异性抗HIV活性。
