5'-linked lipid-oligodeoxyridonucleotide derivatives as inhibitors of human immunodeficiency virus replication.
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.
Kim
S G
SG
Department of Industrial Chemistry, Chiba Institute of Technology, Japan.
Nakashima
H
H
Shoji
Y
Y
Inagawa
T
T
Yamamoto
N
N
Kinzuka
Y
Y
Takai
K
K
Takaku
H
H
D001483:Base Sequence; D002461:Cell Line, Transformed / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D006678:HIV / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D012194:RNA-Directed DNA Polymerase / Q000187:drug effects* / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects* / Q000502:physiology
D009838:Oligodeoxyribonucleotides; D010743:Phospholipids; D012194:RNA-Directed DNA Polymerase