Abstract
3-Nitropyrrole (M) was introduced as a non-discriminating 'universal' base in nucleic acid duplexes by virtue of small size and a presumed tendency to stack but not hydrogen bond with canonical bases. However, the absence of thermally-induced hyperchromic changes by single-stranded deoxyoligomers in which M alternates with A or C residues shows that M does not stack strongly with A or C nearest neighbors. Yet, the insertion of a centrally located M opposite any canonical base in a duplex is sometimes even less destabilizing than that of some mismatches, and the variation in duplex stability is small. In triplexes, on the other hand, an M residue centrally located in the third strand reduces triplex stability drastically even when the X.Y target base pair is A.T or G. C in a homopurine. homopyrimidine segment. But, when the target duplex opposition is M-T and the third strand residue is T, the presence of M in the test triplet has little effect on triplex stability. Therefore, a lack of hydrogen bonding in an otherwise helix-compatible test triplet cannot be responsible for triplex destabilization when M is the third strand residue. Thus, M is non-discriminating and none-too-destabilizing in a duplex, but in a triplex it is extremely destabilizing when in the third strand.
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Selected References
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- Berressem R., Engels J. W. 6-Oxocytidine a novel protonated C-base analogue for stable triple helix formation. Nucleic Acids Res. 1995 Sep 11;23(17):3465–3472. doi: 10.1093/nar/23.17.3465. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blake R. D., Massoulié J., Fresco J. R. Polynucleotides. 8. A spectral approach to the equilibria between polyriboadenylate and polyribouridylate and their complexes. J Mol Biol. 1967 Dec 14;30(2):291–308. [PubMed] [Google Scholar]
- Brahms J., Maurizot J. C., Michelson A. M. Conformation and thermodynamic properties of oligocytidylic acids. J Mol Biol. 1967 May 14;25(3):465–480. doi: 10.1016/0022-2836(67)90199-4. [DOI] [PubMed] [Google Scholar]
- Brahms J., Michelson A. M., Van Holde K. E. Adenylate oligomers in single- and double-strand conformation. J Mol Biol. 1966 Feb;15(2):467–488. doi: 10.1016/s0022-2836(66)80122-5. [DOI] [PubMed] [Google Scholar]
- Dolinnaya N. G., Ulku A., Fresco J. R. Parallel-stranded linear homoduplexes of d(A+-G)n > 10 and d(A-G)n > 10 manifesting the contrasting ionic strength sensitivities of poly(A+.A+) and DNA. Nucleic Acids Res. 1997 Mar 15;25(6):1100–1107. doi: 10.1093/nar/25.6.1100. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Durland R. H., Rao T. S., Bodepudi V., Seth D. M., Jayaraman K., Revankar G. R. Azole substituted oligonucleotides promote antiparallel triplex formation at non-homopurine duplex targets. Nucleic Acids Res. 1995 Feb 25;23(4):647–653. doi: 10.1093/nar/23.4.647. [DOI] [PMC free article] [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]
- Fossella J. A., Kim Y. J., Shih H., Richards E. G., Fresco J. R. Relative specificities in binding of Watson-Crick base pairs by third strand residues in a DNA pyrimidine triplex motif. Nucleic Acids Res. 1993 Sep 25;21(19):4511–4515. doi: 10.1093/nar/21.19.4511. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Izant J. G., Weintraub H. Inhibition of thymidine kinase gene expression by anti-sense RNA: a molecular approach to genetic analysis. Cell. 1984 Apr;36(4):1007–1015. doi: 10.1016/0092-8674(84)90050-3. [DOI] [PubMed] [Google Scholar]
- Kiessling L. L., Griffin L. C., Dervan P. B. Flanking sequence effects within the pyrimidine triple-helix motif characterized by affinity cleaving. Biochemistry. 1992 Mar 17;31(10):2829–2834. doi: 10.1021/bi00125a026. [DOI] [PubMed] [Google Scholar]
- Marky L. A., Breslauer K. J. Calculating thermodynamic data for transitions of any molecularity from equilibrium melting curves. Biopolymers. 1987 Sep;26(9):1601–1620. doi: 10.1002/bip.360260911. [DOI] [PubMed] [Google Scholar]
- Mizuno T., Chou M. Y., Inouye M. A unique mechanism regulating gene expression: translational inhibition by a complementary RNA transcript (micRNA). Proc Natl Acad Sci U S A. 1984 Apr;81(7):1966–1970. doi: 10.1073/pnas.81.7.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nichols R., Andrews P. C., Zhang P., Bergstrom D. E. A universal nucleoside for use at ambiguous sites in DNA primers. Nature. 1994 Jun 9;369(6480):492–493. doi: 10.1038/369492a0. [DOI] [PubMed] [Google Scholar]
- Pilch D. S., Brousseau R., Shafer R. H. Thermodynamics of triple helix formation: spectrophotometric studies on the d(A)10.2d(T)10 and d(C+3T4C+3).d(G3A4G3).d(C3T4C3) triple helices. Nucleic Acids Res. 1990 Oct 11;18(19):5743–5750. doi: 10.1093/nar/18.19.5743. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang G., Levy D. D., Seidman M. M., Glazer P. M. Targeted mutagenesis in mammalian cells mediated by intracellular triple helix formation. Mol Cell Biol. 1995 Mar;15(3):1759–1768. doi: 10.1128/mcb.15.3.1759. [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]