Abstract
The potential use of alpha-beta-anomeric duplex oligonucleotides to inhibit transcription factor activity by the decoy approach is investigated in this report. Indeed, several alpha-beta-anomeric heteroduplexes display a sequence-specific interaction with the p50 subunit of the transcription factor NF kappa B. Used in a decoy approach, these duplexes interact strongly enough with this transcription factor to modulate the expression of a reporter gene, under the control of NF kappa B. However, all the alpha-beta-anomeric heteroduplexes do not interact with the p50 subunit; the sequence of the chirally natural beta-anomeric strand may explain the different recognition properties of the protein. The analysis of the appropriate beta-anomeric sequences is consistent with a preferential interaction of the p50 subunit with one strand of double-stranded DNA.
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- Agrawal S., Temsamani J., Tang J. Y. Pharmacokinetics, biodistribution, and stability of oligodeoxynucleotide phosphorothioates in mice. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7595–7599. doi: 10.1073/pnas.88.17.7595. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bertrand J. R., Rayner B., Imbach J. L., Paoletti C., Malvy C. Comparative activity of alpha- and beta-anomeric oligonucleotides on rabbit beta globin synthesis: inhibitory effect of cap targeted alpha-oligonucleotides. Biochem Biophys Res Commun. 1989 Oct 16;164(1):311–318. doi: 10.1016/0006-291x(89)91719-1. [DOI] [PubMed] [Google Scholar]
- Bielinska A., Shivdasani R. A., Zhang L. Q., Nabel G. J. Regulation of gene expression with double-stranded phosphorothioate oligonucleotides. Science. 1990 Nov 16;250(4983):997–1000. doi: 10.1126/science.2237444. [DOI] [PubMed] [Google Scholar]
- Bloch E., Lavignon M., Bertrand J. R., Pognan F., Morvan F., Malvy C., Rayner B., Imbach J. L., Paoletti C. Alpha-anomeric DNA: beta-RNA hybrids as new synthetic inhibitors of Escherichia coli RNase H, Drosophila embryo RNase H and M-MLV reverse transcriptase. Gene. 1988 Dec 10;72(1-2):349–360. doi: 10.1016/0378-1119(88)90162-x. [DOI] [PubMed] [Google Scholar]
- Cazenave C., Chevrier M., Nguyen T. T., Hélène C. Rate of degradation of [alpha]- and [beta]-oligodeoxynucleotides in Xenopus oocytes. Implications for anti-messenger strategies. Nucleic Acids Res. 1987 Dec 23;15(24):10507–10521. doi: 10.1093/nar/15.24.10507. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen C., Okayama H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol. 1987 Aug;7(8):2745–2752. doi: 10.1128/mcb.7.8.2745. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clusel C., Ugarte E., Enjolras N., Vasseur M., Blumenfeld M. Ex vivo regulation of specific gene expression by nanomolar concentration of double-stranded dumbbell oligonucleotides. Nucleic Acids Res. 1993 Jul 25;21(15):3405–3411. doi: 10.1093/nar/21.15.3405. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cohen J. S. Oligonucleotides as therapeutic agents. Pharmacol Ther. 1991 Nov;52(2):211–225. doi: 10.1016/0163-7258(91)90009-b. [DOI] [PubMed] [Google Scholar]
- Gagnor C., Bertrand J. R., Thenet S., Lemaître M., Morvan F., Rayner B., Malvy C., Lebleu B., Imbach J. L., Paoletti C. alpha-DNA. VI: Comparative study of alpha- and beta-anomeric oligodeoxyribonucleotides in hybridization to mRNA and in cell free translation inhibition. Nucleic Acids Res. 1987 Dec 23;15(24):10419–10436. doi: 10.1093/nar/15.24.10419. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goodchild J. Antisense antivirals. Antisense Res Dev. 1991 Winter;1(4):361–364. doi: 10.1089/ard.1991.1.361. [DOI] [PubMed] [Google Scholar]
- Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Higgins K. A., Perez J. R., Coleman T. A., Dorshkind K., McComas W. A., Sarmiento U. M., Rosen C. A., Narayanan R. Antisense inhibition of the p65 subunit of NF-kappa B blocks tumorigenicity and causes tumor regression. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9901–9905. doi: 10.1073/pnas.90.21.9901. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hélène C. Rational design of sequence-specific oncogene inhibitors based on antisense and antigene oligonucleotides. Eur J Cancer. 1991;27(11):1466–1471. doi: 10.1016/0277-5379(91)90033-a. [DOI] [PubMed] [Google Scholar]
- Hélène C., Toulmé J. J. Specific regulation of gene expression by antisense, sense and antigene nucleic acids. Biochim Biophys Acta. 1990 Jun 21;1049(2):99–125. doi: 10.1016/0167-4781(90)90031-v. [DOI] [PubMed] [Google Scholar]
- Kieran M., Blank V., Logeat F., Vandekerckhove J., Lottspeich F., Le Bail O., Urban M. B., Kourilsky P., Baeuerle P. A., Israël A. The DNA binding subunit of NF-kappa B is identical to factor KBF1 and homologous to the rel oncogene product. Cell. 1990 Sep 7;62(5):1007–1018. doi: 10.1016/0092-8674(90)90275-j. [DOI] [PubMed] [Google Scholar]
- Lancelot G., Guesnet J. L., Vovelle F. Solution structure of the parallel-stranded duplex oligonucleotide alpha-d(TCTAAAC)-beta-d(AGATTTG) via complete relaxation matrix analysis of the NOE effects and molecular mechanics calculations. Biochemistry. 1989 Sep 19;28(19):7871–7878. doi: 10.1021/bi00445a049. [DOI] [PubMed] [Google Scholar]
- Lilienbaum A., Duc Dodon M., Alexandre C., Gazzolo L., Paulin D. Effect of human T-cell leukemia virus type I tax protein on activation of the human vimentin gene. J Virol. 1990 Jan;64(1):256–263. doi: 10.1128/jvi.64.1.256-263.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lilienbaum A., Paulin D. Activation of the human vimentin gene by the Tax human T-cell leukemia virus. I. Mechanisms of regulation by the NF-kappa B transcription factor. J Biol Chem. 1993 Jan 25;268(3):2180–2188. [PubMed] [Google Scholar]
- Meisterernst M., Gander I., Rogge L., Winnacker E. L. A quantitative analysis of nuclear factor I/DNA interactions. Nucleic Acids Res. 1988 May 25;16(10):4419–4435. doi: 10.1093/nar/16.10.4419. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morvan F., Rayner B., Imbach J. L., Chang D. K., Lown J. W. alpha-DNA. I. Synthesis, characterization by high field 1H-NMR, and base-pairing properties of the unnatural hexadeoxyribonucleotide alpha-[d(CpCpTpTpCpC)] with its complement beta-[d(GpGpApApGpG)]. Nucleic Acids Res. 1986 Jun 25;14(12):5019–5035. doi: 10.1093/nar/14.12.5019. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morvan F., Rayner B., Leonetti J. P., Imbach J. L. alpha-DNA. VII. Solid phase synthesis of alpha-anomeric oligodeoxyribonucleotides. Nucleic Acids Res. 1988 Feb 11;16(3):833–847. doi: 10.1093/nar/16.3.833. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Paoletti J., Bazile D., Morvan F., Imbach J. L., Paoletti C. Alpha-DNA VIII: thermodynamic parameters of complexes formed between the oligo-alpha-deoxynucleotides: alpha-d(GGAAGG) and alpha-d(CCTTCC) and their complementary oligo-beta-deoxynucleotides: beta-d(CCTTCC) and beta-d(GGAAGG) are different. Nucleic Acids Res. 1989 Apr 11;17(7):2693–2704. doi: 10.1093/nar/17.7.2693. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Petersheim M., Turner D. H. Base-stacking and base-pairing contributions to helix stability: thermodynamics of double-helix formation with CCGG, CCGGp, CCGGAp, ACCGGp, CCGGUp, and ACCGGUp. Biochemistry. 1983 Jan 18;22(2):256–263. doi: 10.1021/bi00271a004. [DOI] [PubMed] [Google Scholar]
- Schreck R., Zorbas H., Winnacker E. L., Baeuerle P. A. The NF-kappa B transcription factor induces DNA bending which is modulated by its 65-kD subunit. Nucleic Acids Res. 1990 Nov 25;18(22):6497–6502. doi: 10.1093/nar/18.22.6497. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith D. B., Johnson K. S. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988 Jul 15;67(1):31–40. doi: 10.1016/0378-1119(88)90005-4. [DOI] [PubMed] [Google Scholar]
- Thanos D., Maniatis T. The high mobility group protein HMG I(Y) is required for NF-kappa B-dependent virus induction of the human IFN-beta gene. Cell. 1992 Nov 27;71(5):777–789. doi: 10.1016/0092-8674(92)90554-p. [DOI] [PubMed] [Google Scholar]
- Thenet S., Morvan F., Bertrand J. R., Gautie C., Malvy C. Alpha are more stable than beta anomer oligonucleotides in 3T3 cellular extracts. Biochimie. 1988 Dec;70(12):1729–1732. doi: 10.1016/0300-9084(88)90031-4. [DOI] [PubMed] [Google Scholar]


