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  • 标题:Site specificity of the inhibitory effects of oligo(nucleoside methylphosphonate)s complementary to the acceptor splice junction of herpes simplex virus type 1 immediate early mRNA 4
  • 本地全文:下载
  • 作者:M Kulka ; C C Smith ; L Aurelian
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:1989
  • 卷号:86
  • 期号:18
  • 页码:6868-6872
  • DOI:10.1073/pnas.86.18.6868
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:Oligo(nucleoside methylphosphonate)s complementary to the splice junction of herpes simplex virus type 1 immediate early pre-mRNAs 4 and 5 caused specific inhibition of herpes simplex virus type 1 growth. The dodecamer d(TpTCCTCCTGCGG) (deoxynucleoside methylphosphonate residues in italic) caused 50% and 98% decreases in herpes simplex virus type 1 titers at concentrations of 15 microM and 100 microM, respectively. d(TpTCCTCCTGCGG) inhibited viral but not cellular protein synthesis and decreased splicing of immediate early pre-mRNAs 4 and 5. Inhibition was highly sequence specific. A psoralen derivative of d(TpTCCTCCTGCGG) that can covalently bind to complementary sequences after exposure to 365-nm irradiation caused 90-98% inhibition of virus growth in cells treated with oligomer (5 microM) and irradiated at 1-3 hr postinfection. The data suggest that oligo(nucleoside methylphosphonate)s of appropriate sequence and derivatization may be effective as antiviral agents.
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