Control of gene expression by oligonucleotides covalently linked to intercalating agents
- PMID: 2687107
- DOI: 10.1139/g89-062
Control of gene expression by oligonucleotides covalently linked to intercalating agents
Abstract
Oligodeoxynucleotides covalently linked to intercalating agents selectively recognize the complementary sequence of the oligonucleotide. The intercalating agent provides an additional binding energy which stabilizes the complex. These substances can be used in vitro to block mRNA translation. In cell cultures they are able to inhibit the cytopathic effect of viruses, such as influenza virus and the oncogenic virus SV40. They kill trypanosomes in culture as a result of protein synthesis inhibition. A reactive group can be attached to an oligodeoxynucleotide in order to achieve site-directed modifications of the target sequence. Metal complexes of EDTA, phenanthroline or porphyrins induce cleavage reactions of the phosphodiester backbone in both DNA and RNA. Photoactive groups can be used to modify bases in the complementary sequence. The double helix can be recognized and modified by oligonucleotides that bind to the major groove, forming a local triple helix. These site-directed modifications may inhibit biological processes. The oligonucleotide can be made resistant to nuclease digestion by substituting the synthetic alpha-anomers of nucleosides to the natural beta-nucleosides. These results provide the basis for the design of gene-specific inhibitors that can be used as tools in molecular and cellular biology. They also suggest new approaches for the rational development of selective anti-viral, anti-parasitic, and anti-tumoral agents.
Similar articles
-
The anti-gene strategy: control of gene expression by triplex-forming-oligonucleotides.Anticancer Drug Des. 1991 Dec;6(6):569-84. Anticancer Drug Des. 1991. PMID: 1772570 Review.
-
Specific inhibition of mRNA translation by complementary oligonucleotides covalently linked to intercalating agents.Proc Natl Acad Sci U S A. 1986 Mar;83(5):1227-31. doi: 10.1073/pnas.83.5.1227. Proc Natl Acad Sci U S A. 1986. PMID: 3513172 Free PMC article.
-
Oligodeoxynucleotides covalently linked to intercalating agents: a new class of gene regulatory substances.Biochimie. 1985 Jul-Aug;67(7-8):777-83. doi: 10.1016/s0300-9084(85)80167-x. Biochimie. 1985. PMID: 3910111
-
Triple-helix formation by alpha oligodeoxynucleotides and alpha oligodeoxynucleotide-intercalator conjugates.Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6023-7. doi: 10.1073/pnas.88.14.6023. Proc Natl Acad Sci U S A. 1991. PMID: 2068079 Free PMC article.
-
[Mechanism for suppression mRNA translation with antisense oligonucleotides].Mol Biol (Mosk). 1990 Sep-Oct;24(5):1157-61. Mol Biol (Mosk). 1990. PMID: 2290415 Review. Russian.
Cited by
-
DNA antisense strategies in the study of receptors for vasoactive peptides, and of growth and wound-healing factors.Mol Cell Biochem. 1997 Jul;172(1-2):199-211. Mol Cell Biochem. 1997. PMID: 9278246 Review.
-
Sequence specific inhibition of DNA restriction enzyme cleavage by PNA.Nucleic Acids Res. 1993 Jan 25;21(2):197-200. doi: 10.1093/nar/21.2.197. Nucleic Acids Res. 1993. PMID: 8382793 Free PMC article.
-
From Bioengineering to CRISPR/Cas9 - A Personal Retrospective of 20 Years of Research in Programmable Genome Targeting.Front Genet. 2018 Jan 26;9:5. doi: 10.3389/fgene.2018.00005. eCollection 2018. Front Genet. 2018. PMID: 29434619 Free PMC article.
-
Tethered naphthalene diimide-based intercalators for DNA triplex stabilization.Nucleic Acids Res. 2000 May 15;28(10):2128-34. doi: 10.1093/nar/28.10.2128. Nucleic Acids Res. 2000. PMID: 10773082 Free PMC article.
-
Preclinical and clinical pharmacology of antisense oligonucleotides.Mol Biotechnol. 1999 Aug;12(1):1-11. doi: 10.1385/MB:12:1:1. Mol Biotechnol. 1999. PMID: 10554769 Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
