Block polycationic oligonucleotide derivative: synthesis and inhibition of herpes virus reproduction.
The block polycationic oligonucleotide (oligo) consisting of a phosphodiester 12-mer linked to the polycation chain at the 3'-end and cholesteryl group at the 5'-end was synthesized. The polycation chain was grown on the solid support using the monomer, H-phosphonate of 1-O-(4,4'-dimethoxytrityl)-1,3-butanediol. Amino groups were introduced in the polymer backbone using 1,4-diaminobutane, and then the oligo chain was formed at the free end of the polymer. The last stage of the synthesis was the attachment of the cholesteryl group to the 5'-end of the oligo prior to cleavage and deprotection of the copolymer. The nucleotide sequence of this copolymer, CGTTCCTCCTGC, was complementary to the splicing site of immediate early (IE) mRNA 4 and 5 of herpes simplex virus type 1 (HSV-1). The stability of the duplexes formed between the copolymer and the complementary 12-mer was similar to that of unmodified oligo. The stability of the block polycationic oligo against phosphodiesterase digestion was significantly increased compared to that of the unmodified oligo. The block polycationic oligo inhibited the reproduction of HSV-1 in Vero cells; however, the effect was significantly less than the effect of 12-mer oligo modified with cholesterol at the 5'-end. The decreased antiviral activity of the copolymer is explained by the polycation-induced stimulation of the virus infection.
Vinogradov
S V
SV
Department of Polymer Sciences, Moscow State University, Russia.
Suzdaltseva
Y G
YG
Kabanov
A V
AV
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001483:Base Sequence; D002522:Chlorocebus aethiops; D002784:Cholesterol; D017781:Genes, Immediate-Early; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis* / Q000494:pharmacology*; D012326:RNA Splicing / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D013329:Structure-Activity Relationship; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D002784:Cholesterol