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Inhibition of Influenza Virus Replication in MDCK Cells by Circular Dumbbell RNA/DNA Chimeras with Closed Alkyl Loop Structures
Author(s) -
Hamazaki Hiroyuki,
Abe Takayuki,
Yamakawa Hidefumi,
Yokota Tomoyuki,
Shigeta Shiro,
Takaku Hiroshi
Publication year - 2002
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(200207)85:7<2183::aid-hlca2183>3.0.co;2-u
Subject(s) - chemistry , dumbbell , dna , influenza a virus , rna , alkyl , circular dna , virus , microbiology and biotechnology , virology , stereochemistry , gene , biochemistry , genome , biology , medicine , organic chemistry , physical therapy
We have demonstrated that a new type of circular dumbbell RNA/DNA chimeric oligonucleotide (CDRDON) with two closed nucleotide or alkyl loop structures (hexa‐ethylene glycol) inhibits influenza virus A replication in MDCK cells. The enzymatic synthesis of circular dumbbell RNA/DNA chimeric oligonucleotides was achieved by enzymatically ligating a self‐complementary phosphorylated oligonucleotide with T4‐RNA ligase. The CDRDON‐Al, with two closed alkyl loop structures, showed higher nuclease resistance, hybridization, and cellular uptake than the anti‐S‐ODN and the CDRDON, with two closed nucleotide hairpin‐loop structures. The circular dumbbell RNA/DNA chimeric oligonucleotide (CDRDON‐Al‐PB2‐as), containing an AUG initiation‐codon sequence as the target of PB2, showed highly inhibitory effects on influenza A virus RNA expression. The limited toxicity of unmodified phosphodiester oligonucleotides and the sequence‐specific binding to target mRNA indicate that circular dumbbell RNA/DNA chimeric phosphodiester oligonucleotides can be used with intact cells, and may prevent viral replication in culture.