Antiviral activity of conjugates between poly(L-lysine) and synthetic oligodeoxyribonucleotides.
Short (14 to 20-mer range) synthetic oligodeoxyribonucleotides (oligos) allow to modulate specifically viral or cellular gene expression at various stages thus providing a versatile tool for fundamental studies and a rational approach to antiviral chemotherapy. Several problems, such as metabolic stability and efficient cell internalization of oligos, still limit this approach appreciably, as briefly discussed here. We demonstrate here that the conjugation of 15-mer (beta)-anomeric oligos to poly(L-lysine) allows a specific protection of various cell lines against vesicular stomatitis virus infection at concentrations lower than 1 microM. This can be achieved with oligos complementary to the viral N-protein mRNA initiation site or to viral intergenic sequences, i.e., to untranscribed regions. No antiviral activity can be obtained with (alpha)-anomeric oligos directed against the same targets, although such analogues are much more resistant to nuclease degradation and form stable hybrids, at least in cell-free experiments.
Leonetti
J P
JP
Laboratories de Biochimie des Protéines, Université de Montpellier II, France.
Rayner
B
B
Lemaitre
M
M
Gagnor
C
C
Milhaud
P G
PG
Imbach
J L
JL
Lebleu
B
B
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D002460:Cell Line; D005796:Genes / Q000187:drug effects; D005814:Genes, Viral / Q000187:drug effects; D007739:L Cells; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D011107:Polylysine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D011107:Polylysine