Abstract
Oligonucleotide-directed triple helix formation is mostly restricted to oligopyrimidine*oligopurine sequences of double helical DNA. An interruption of one or two pyrimidines in the oligopurine target strand leads to a strong triplex destabilisation. We have investigated the effect of nucleotide analogues introduced in the third strand at the site opposite the base pair inversion(s). We show that a 3-nitropyrrole derivative (M) discriminates G*C from C*G, A*T and T*A in the presence of a triplex-specific ligand (a benzo[e]pyridoindole derivative, BePI). N6-methoxy-2,6-diaminopurine (K) binds to an A*T base pair better than a T*A, G*C or C*G base pair. Some discrimination is still observed in the presence of BePI and triplex stability is markedly increased. These findings should help in designing BePI-oligonucleotide conjugates to extend the range of DNA sequences available for triplex formation.
Full Text
The Full Text of this article is available as a PDF (81.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Amosova O., George J., Fresco J. R. Effect of the 1-(2'-deoxy-beta-D-ribofuranosyl)-3-nitropyrrole residue on the stability of DNA duplexes and triplexes. Nucleic Acids Res. 1997 May 15;25(10):1930–1934. doi: 10.1093/nar/25.10.1930. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Beal P. A., Dervan P. B. Second structural motif for recognition of DNA by oligonucleotide-directed triple-helix formation. Science. 1991 Mar 15;251(4999):1360–1363. doi: 10.1126/science.2003222. [DOI] [PubMed] [Google Scholar]
- Belotserkovskii B. P., Veselkov A. G., Filippov S. A., Dobrynin V. N., Mirkin S. M., Frank-Kamenetskii M. D. Formation of intramolecular triplex in homopurine-homopyrimidine mirror repeats with point substitutions. Nucleic Acids Res. 1990 Nov 25;18(22):6621–6624. doi: 10.1093/nar/18.22.6621. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brown D. M., Hewlins M. J., Schell P. The tautomeric state of N(4)-hydroxy- and of N(4)-amino-cytosine derivatives. J Chem Soc Perkin 1. 1968;15:1925–1929. doi: 10.1039/j39680001925. [DOI] [PubMed] [Google Scholar]
- Brown D. M., Lin P. K. Synthesis and duplex stability of oligonucleotides containing adenine-guanine analogues. Carbohydr Res. 1991 Sep 2;216:129–139. doi: 10.1016/0008-6215(92)84156-m. [DOI] [PubMed] [Google Scholar]
- Cantor C. R., Warshaw M. M., Shapiro H. Oligonucleotide interactions. 3. Circular dichroism studies of the conformation of deoxyoligonucleotides. Biopolymers. 1970;9(9):1059–1077. doi: 10.1002/bip.1970.360090909. [DOI] [PubMed] [Google Scholar]
- Chandler S. P., Strekowski L., Wilson W. D., Fox K. R. Footprinting studies on ligands which stabilize DNA triplexes: effects on stringency within a parallel triple helix. Biochemistry. 1995 May 30;34(21):7234–7242. doi: 10.1021/bi00021a039. [DOI] [PubMed] [Google Scholar]
- Cooney M., Czernuszewicz G., Postel E. H., Flint S. J., Hogan M. E. Site-specific oligonucleotide binding represses transcription of the human c-myc gene in vitro. Science. 1988 Jul 22;241(4864):456–459. doi: 10.1126/science.3293213. [DOI] [PubMed] [Google Scholar]
- Duval-Valentin G., Thuong N. T., Hélène C. Specific inhibition of transcription by triple helix-forming oligonucleotides. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):504–508. doi: 10.1073/pnas.89.2.504. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Escudé C., Sun J. S., Nguyen C. H., Bisagni E., Garestier T., Hélène C. Ligand-induced formation of triple helices with antiparallel third strands containing G and T. Biochemistry. 1996 May 7;35(18):5735–5740. doi: 10.1021/bi960120c. [DOI] [PubMed] [Google Scholar]
- Fox K. R., Polucci P., Jenkins T. C., Neidle S. A molecular anchor for stabilizing triple-helical DNA. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7887–7891. doi: 10.1073/pnas.92.17.7887. [DOI] [PMC free article] [PubMed] [Google Scholar]
- François J. C., Saison-Behmoaras T., Thuong N. T., Hélène C. Inhibition of restriction endonuclease cleavage via triple helix formation by homopyrimidine oligonucleotides. Biochemistry. 1989 Dec 12;28(25):9617–9619. doi: 10.1021/bi00451a011. [DOI] [PubMed] [Google Scholar]
- Giovannangéli C., Rougée M., Garestier T., Thuong N. T., Hélène C. Triple-helix formation by oligonucleotides containing the three bases thymine, cytosine, and guanine. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8631–8635. doi: 10.1073/pnas.89.18.8631. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gowers D. M., Fox K. R. DNA triple helix formation at oligopurine sites containing multiple contiguous pyrimidines. Nucleic Acids Res. 1997 Oct 1;25(19):3787–3794. doi: 10.1093/nar/25.19.3787. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Griffin L. C., Dervan P. B. Recognition of thymine adenine.base pairs by guanine in a pyrimidine triple helix motif. Science. 1989 Sep 1;245(4921):967–971. doi: 10.1126/science.2549639. [DOI] [PubMed] [Google Scholar]
- Grigoriev M., Praseuth D., Robin P., Hemar A., Saison-Behmoaras T., Dautry-Varsat A., Thuong N. T., Hélène C., Harel-Bellan A. A triple helix-forming oligonucleotide-intercalator conjugate acts as a transcriptional repressor via inhibition of NF kappa B binding to interleukin-2 receptor alpha-regulatory sequence. J Biol Chem. 1992 Feb 15;267(5):3389–3395. [PubMed] [Google Scholar]
- Hill F., Williams D. M., Loakes D., Brown D. M. Comparative mutagenicities of N6-methoxy-2,6-diaminopurine and N6-methoxyaminopurine 2'-deoxyribonucleosides and their 5'-triphosphates. Nucleic Acids Res. 1998 Mar 1;26(5):1144–1149. doi: 10.1093/nar/26.5.1144. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hélène C. The anti-gene strategy: control of gene expression by triplex-forming-oligonucleotides. Anticancer Drug Des. 1991 Dec;6(6):569–584. [PubMed] [Google Scholar]
- Kukreti S., Sun J. S., Garestier T., Hélène C. Extension of the range of DNA sequences available for triple helix formation: stabilization of mismatched triplexes by acridine-containing oligonucleotides. Nucleic Acids Res. 1997 Nov 1;25(21):4264–4270. doi: 10.1093/nar/25.21.4264. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Le Doan T., Perrouault L., Praseuth D., Habhoub N., Decout J. L., Thuong N. T., Lhomme J., Hélène C. Sequence-specific recognition, photocrosslinking and cleavage of the DNA double helix by an oligo-[alpha]-thymidylate covalently linked to an azidoproflavine derivative. Nucleic Acids Res. 1987 Oct 12;15(19):7749–7760. doi: 10.1093/nar/15.19.7749. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee J. S., Latimer L. J., Hampel K. J. Coralyne binds tightly to both T.A.T- and C.G.C(+)-containing DNA triplexes. Biochemistry. 1993 Jun 1;32(21):5591–5597. doi: 10.1021/bi00072a014. [DOI] [PubMed] [Google Scholar]
- Lin P. K., Brown D. M. Synthesis and duplex stability of oligonucleotides containing cytosine-thymine analogues. Nucleic Acids Res. 1989 Dec 25;17(24):10373–10383. doi: 10.1093/nar/17.24.10373. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Loakes D., Brown D. M. 5-Nitroindole as an universal base analogue. Nucleic Acids Res. 1994 Oct 11;22(20):4039–4043. doi: 10.1093/nar/22.20.4039. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maher L. J., 3rd, Dervan P. B., Wold B. Analysis of promoter-specific repression by triple-helical DNA complexes in a eukaryotic cell-free transcription system. Biochemistry. 1992 Jan 14;31(1):70–81. doi: 10.1021/bi00116a012. [DOI] [PubMed] [Google Scholar]
- Maher L. J., 3rd Prospects for the therapeutic use of antigene oligonucleotides. Cancer Invest. 1996;14(1):66–82. doi: 10.3109/07357909609018437. [DOI] [PubMed] [Google Scholar]
- Maher L. J., 3rd, Wold B., Dervan P. B. Inhibition of DNA binding proteins by oligonucleotide-directed triple helix formation. Science. 1989 Aug 18;245(4919):725–730. doi: 10.1126/science.2549631. [DOI] [PubMed] [Google Scholar]
- Mergny J. L., Collier D., Rougée M., Montenay-Garestier T., Hélène C. Intercalation of ethidium bromide into a triple-stranded oligonucleotide. Nucleic Acids Res. 1991 Apr 11;19(7):1521–1526. doi: 10.1093/nar/19.7.1521. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mergny J. L., Duval-Valentin G., Nguyen C. H., Perrouault L., Faucon B., Rougée M., Montenay-Garestier T., Bisagni E., Hélène C. Triple helix-specific ligands. Science. 1992 Jun 19;256(5064):1681–1684. doi: 10.1126/science.256.5064.1681. [DOI] [PubMed] [Google Scholar]
- Mergny J. L., Sun J. S., Rougée M., Montenay-Garestier T., Barcelo F., Chomilier J., Hélène C. Sequence specificity in triple-helix formation: experimental and theoretical studies of the effect of mismatches on triplex stability. Biochemistry. 1991 Oct 8;30(40):9791–9798. doi: 10.1021/bi00104a031. [DOI] [PubMed] [Google Scholar]
- Moser H. E., Dervan P. B. Sequence-specific cleavage of double helical DNA by triple helix formation. Science. 1987 Oct 30;238(4827):645–650. doi: 10.1126/science.3118463. [DOI] [PubMed] [Google Scholar]
- Nedderman A. N., Stone M. J., Williams D. H., Lin P. K., Brown D. M. Molecular basis for methoxyamine-initiated mutagenesis: 1H nuclear magnetic resonance studies of oligonucleotide duplexes containing base-modified cytosine residues. J Mol Biol. 1993 Apr 5;230(3):1068–1076. doi: 10.1006/jmbi.1993.1219. [DOI] [PubMed] [Google Scholar]
- Nguyen C. H., Lhoste J. M., Lavelle F., Bissery M. C., Bisagni E. Synthesis and antitumor activity of 1-[[(dialkylamino)alkyl]amino]-4-methyl-5H-pyrido[4,3-b]benzo[e]- and -benzo[g])indoles. A new class of antineoplastic agents. J Med Chem. 1990 May;33(5):1519–1528. doi: 10.1021/jm00167a037. [DOI] [PubMed] [Google Scholar]
- Pilch D. S., Levenson C., Shafer R. H. Structure, stability, and thermodynamics of a short intermolecular purine-purine-pyrimidine triple helix. Biochemistry. 1991 Jun 25;30(25):6081–6088. doi: 10.1021/bi00239a001. [DOI] [PubMed] [Google Scholar]
- Radhakrishnan I., Patel D. J., Gao X. Three-dimensional homonuclear NOESY-TOCSY of an intramolecular pyrimidine.purine.pyrimidine DNA triplex containing a central G.TA triple: nonexchangeable proton assignments and structural implications. Biochemistry. 1992 Mar 10;31(9):2514–2523. doi: 10.1021/bi00124a011. [DOI] [PubMed] [Google Scholar]
- Rajagopal P., Feigon J. Triple-strand formation in the homopurine:homopyrimidine DNA oligonucleotides d(G-A)4 and d(T-C)4. Nature. 1989 Jun 22;339(6226):637–640. doi: 10.1038/339637a0. [DOI] [PubMed] [Google Scholar]
- Roberts R. W., Crothers D. M. Specificity and stringency in DNA triplex formation. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9397–9401. doi: 10.1073/pnas.88.21.9397. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scaria P. V., Shafer R. H. Binding of ethidium bromide to a DNA triple helix. Evidence for intercalation. J Biol Chem. 1991 Mar 25;266(9):5417–5423. [PubMed] [Google Scholar]
- Silver G. C., Nguyen C. H., Boutorine A. S., Bisagni E., Garestier T., Hélène C. Conjugates of oligonucleotides with triplex-specific intercalating agents. Stabilization of triple-helical DNA in the promoter region of the gene for the alpha-subunit of interleukin 2 (IL-2R alpha). Bioconjug Chem. 1997 Jan-Feb;8(1):15–22. doi: 10.1021/bc9600675. [DOI] [PubMed] [Google Scholar]
- Sun J. S., De Bizemont T., Duval-Valentin G., Montenay-Garestier T., Hélène C. Extension of the range of recognition sequences for triple helix formation by oligonucleotides containing guanines and thymines. C R Acad Sci III. 1991;313(13):585–590. [PubMed] [Google Scholar]
- Sun J. S., Garestier T., Hélène C. Oligonucleotide directed triple helix formation. Curr Opin Struct Biol. 1996 Jun;6(3):327–333. doi: 10.1016/s0959-440x(96)80051-0. [DOI] [PubMed] [Google Scholar]
- Wang E., Koshlap K. M., Gillespie P., Dervan P. B., Feigon J. Solution structure of a pyrimidine-purine-pyrimidine triplex containing the sequence-specific intercalating non-natural base D3. J Mol Biol. 1996 Apr 19;257(5):1052–1069. doi: 10.1006/jmbi.1996.0223. [DOI] [PubMed] [Google Scholar]
- Wilson W. D., Mizan S., Tanious F. A., Yao S., Zon G. The interaction of intercalators and groove-binding agents with DNA triple-helical structures: the influence of ligand structure, DNA backbone modifications and sequence. J Mol Recognit. 1994 Jun;7(2):89–98. doi: 10.1002/jmr.300070206. [DOI] [PubMed] [Google Scholar]
- Yoon K., Hobbs C. A., Koch J., Sardaro M., Kutny R., Weis A. L. Elucidation of the sequence-specific third-strand recognition of four Watson-Crick base pairs in a pyrimidine triple-helix motif: T.AT, C.GC, T.CG, and G.TA. Proc Natl Acad Sci U S A. 1992 May 1;89(9):3840–3844. doi: 10.1073/pnas.89.9.3840. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Young S. L., Krawczyk S. H., Matteucci M. D., Toole J. J. Triple helix formation inhibits transcription elongation in vitro. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10023–10026. doi: 10.1073/pnas.88.22.10023. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de Bizemont T., Duval-Valentin G., Sun J. S., Bisagni E., Garestier T., Hélène C. Alternate strand recognition of double-helical DNA by (T,G)-containing oligonucleotides in the presence of a triple helix-specific ligand. Nucleic Acids Res. 1996 Mar 15;24(6):1136–1143. doi: 10.1093/nar/24.6.1136. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de los Santos C., Rosen M., Patel D. NMR studies of DNA (R+)n.(Y-)n.(Y+)n triple helices in solution: imino and amino proton markers of T.A.T and C.G.C+ base-triple formation. Biochemistry. 1989 Sep 5;28(18):7282–7289. doi: 10.1021/bi00444a021. [DOI] [PubMed] [Google Scholar]