Phosphorothioate analogues of oligodeoxyribonucleotide: synthesis and activity as inhibitors of replication of human immunodeficiency virus.
The modifications of oligodeoxyribonucleotides include replacement of the other chain either all-PS (S-ODNs), or end-capped with several PS (SO-ODNs) groups at both 3'- and 5'-ends. A general synthesis of phosphorothioate analogues of oligodeoxyribonucleotides is described using the new phosphite. In assays of HIV, oligomers (S-ODNs) with complete replacement of phosphodiesters with phosphorothioate groups were found to be very active. Finally of particular interest is S-ODNs-rev or tat (20mers) which possessed slightly higher anti-HIV activity than S-dC28 itself. By contrast, the unmodified oligomers (ODNs) as well as SO-ODNs did not have any inhibitory effect.
Department of Industrial Chemistry, Chiba Institute of Technology, Japan.
S G
SG
Kim
Y
Y
Suzuki
H
H
Nakashima
N
N
Yamamoto
H
H
Takaku
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001483:Base Sequence; D002460:Cell Line; D003851:Deoxyribonucleases / Q000378:metabolism; D005814:Genes, Viral; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D009838:Oligodeoxyribonucleotides; D003851:Deoxyribonucleases