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Thrombin-binding DNA aptamer forms a unimolecular quadruplex structure in solution.
Open accessAbstract
We have used two-dimensional 1H NMR spectroscopy to study the conformation of the thrombin-binding aptamer d(GGTTGGTGTGGTTGG) in solution. This is one of a series of thrombin-binding DNA aptamers with a consensus 15-base sequence that was recently isolated and shown to inhibit thrombin-catalyzed fibrin clot formation in vitro [Bock, L. C., Griffin, L. C., Latham, J. A., Vermaas, E. H. & Toole, J. J. (1992) Nature (London) 355, 564-566]. The oligonucleotide forms a unimolecular DNA quadruplex consisting of two G-quartets connected by two TT loops and one TGT loop. A potential T.T bp is formed between the two TT loops across the diagonal of the top G-quartet. Thus, all of the invariant bases in the consensus sequence are base-paired. This aptamer structure was determined by NMR and illustrates that this molecule forms a specific folded structure. Knowledge of this structure may be used in the further development of oligonucleotide-based thrombin inhibitors.
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Citations
Cited by
Adaptive Recognition by Nucleic Acid Aptamers
Hermann, T., & Patel, D. J. (2000) · Science · doi:10.1126/science.287.5454.820 · Cited by 1,650
In Vitro Selection of Functional Nucleic Acids
Wilson, D. S., & Szostak, J. W. (1999) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.68.1.611 · Cited by 1,206
Discovery and development of the G-rich oligonucleotide AS1411 as a novel treatment for cancer
Bates, P. J., Laber, D. A., Miller, D. M., Thomas, S. D., & Trent, J. O. (2009) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2009.01.004 · Cited by 874
Following G‐quartet formation by UV‐spectroscopy
Mergny, J.-L., Phan, A.-T., & Lacroix, L. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)01043-6 · Cited by 721
Electrochemistry of Nucleic Acids
Paleček, E., & Bartošík, M. (2012) · Chemical Reviews · doi:10.1021/cr200303p · Cited by 668
Metadata
- Authors
- Macaya, R. F., Schultze, P., Smith, F. W., Roe, J. A., & Feigon, J.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1993-04-15
- Volume
- 90
- Issue
- 8
- Pages
- 3745-3749
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2039658297
- Cited by
- 887
- References
- 0
- FWCI
- 6.25
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Macaya, R. F., Schultze, P., Smith, F. W., Roe, J. A., & Feigon, J. (1993). Thrombin-binding DNA aptamer forms a unimolecular quadruplex structure in solution. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.90.8.3745
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