Inhibitory properties of double-helix-forming circular oligonucleotides.
Several circular oligonucleotides were synthesized and characterized by electrospray ionization mass spectrometry. Experiments on termination of primer extension catalysed by DNA polymerases, Klenow fragment and Tth have demonstrated that a double helix forming circular 2'-deoxyribooligomer containing a 25mer sequence complementary to the target single-stranded DNA along with a 34mer random mismatching stretch appears to be a potent inhibitor of replication in vitro. Studies on inhibition of luciferase gene expression in a cell-free transcription-translation system have shown that a duplex forming circular 2'-deoxyribooligonucleotide containing a 25mer sequence complementary to the target mRNA and a 14mer random mismatching stretch can serve as an effective antisense compound as a standard linear complementary oligomer. Features of double helix forming circular oligonucleotides composed of 2'-deoxyribonucleosides seem to be useful for the design of new antigene and antisense agents.
Azhayeva
E
E
Department of Pharmaceutical Chemistry, University of Kuopio, FIN-70211 Kuopio, Finland.
Azhayev
A
A
Auriola
S
S
Tengvall
U
U
Urtti
A
A
Lönnberg
D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D004256:DNA Polymerase I / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects*; D004277:DNA, Single-Stranded / Q000235:genetics; D018390:Gene Targeting / Q000379:methods*; D017930:Genes, Reporter; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D013698:Templates, Genetic
D004277:DNA, Single-Stranded; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D008156:Luciferases; D004256:DNA Polymerase I