Helix-stabilizing agent, CC-1065, enhances suppression of translation by an antisense oligodeoxynucleotide.
The antitumor antibiotic CC-1065 is known to bind at selected sequences in the minor groove of duplex nucleic acids and to hyperstabilize the duplexes against thermal melting. These properties suggested that CC-1065 may enhance translation inhibition by antisense oligonucleotides directed against a specific mRNA. A 585 bp mRNA transcript containing the equine infectious anemia virus (EIAV) S2 gene and a portion of the env gene was prepared. Also, a complementary 20 mer antisense oligodeoxynucleotide (5'-TGTTGGGTAATAGG-GGTTGA-3') was prepared against a target sequence in the mRNA located near the translational initiation sites of the overlapping S2 and env genes. The center of the target sequence had an expected CC-1065 recognition sequence (5'-UAUUA-3'). Translation in the presence of CC-1065 and antisense was markedly suppressed compared with that of antisense alone. Addition of a sense 20 mer strand, with or without CC-1065, had little or no effect on translation. CC-1065 and related compounds may be useful as ligands for enhancing the stability of sense-antisense duplexes and for promoting the inhibition of translation by antisense oligonucleotides.
Kim
D Y
DY
Department of Veterinary Pathology, School of Veterinary Medicine, Louisiana State University, Baton Rouge 70803, USA.
Swenson
D H
DH
Cho
D Y
DY
Taylor
H W
HW
Shih
D S
DS
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001483:Base Sequence; D004357:Drug Synergism; D000080890:Duocarmycins; D005814:Genes, Viral; D007211:Indoles; D004860:Infectious Anemia Virus, Equine / Q000235:genetics; D007933:Leucomycins / Q000494:pharmacology*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000187:drug effects*; D013489:Suppression, Genetic / Q000187:drug effects*
D000903:Antibiotics, Antineoplastic; D000080890:Duocarmycins; D007211:Indoles; D007933:Leucomycins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; C018782:CC 1065