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The application of a modified nucleotide in aptamer selection: novel thrombin aptamers containing -(1 -pentynyl)-2′-deoxyuridine
Open accessAbstract
Combinatorial libraries of nucleic acids are developing into novel sources for lead compounds in drug development. In order to diversify the pool of ss DNA sequences, we have used a modified nucleotide, 5-(1-pentynyl)-2'-deoxyuridine, in place of thymidine in a random nucleic acid library and screened this library against human thrombin. Previously, we described this screening method to identify a novel structural inhibitor (an aptamer) of the coagulation protease thrombin (Bock, L. et. al. (1992) Nature 355 564-566). Using the modified nucleic acid library, we have now isolated a second pool of thrombin inhibitors with strikingly different sequence composition compared to the selection using natural bases. This second class of aptamers is dependent on the presence of the modified nucleotide for protein binding and clotting inhibition. Our method represents a potential strategy to enhance the diversity of libraries for in vitro selection, and thereby increasing the utility of this technique in the identification of molecules with novel biochemical properties.
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Citations
Cited by
Benner, S. A., & Sismour, A. M. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1637 · Cited by 834
The Chemical Biology of Aptamers
Mayer, G. (2009) · Angewandte Chemie International Edition · doi:10.1002/anie.200804643 · Cited by 592
Li, X., & Liu, D. R. (2004) · Angewandte Chemie International Edition · doi:10.1002/anie.200400656 · Cited by 538
Rohloff, J. C., Gelinas, A. D., Jarvis, T. C., Ochsner, U. A., Schneider, D. J., Gold, L., & Janjic, N. (2014) · Molecular Therapy - Nucleic Acids · doi:10.1038/mtna.2014.49 · Cited by 533
Nucleic Acid Selection and the Challenge of Combinatorial Chemistry
Osborne, S. E., & Ellington, A. D. (1997) · Chemical Reviews · doi:10.1021/cr960009c · Cited by 520
Metadata
- Authors
- Latham, J. A., Johnson, R., & Toole, J. J.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 1994
- Volume
- 22
- Issue
- 14
- Pages
- 2817-2822
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- OpenAlex
- W2041082927
- Cited by
- 200
- References
- 0
- FWCI
- 2.70
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: The application of a modified nucleotide in aptamer selection: novel thrombin aptamers containing -(1 -pentynyl)-2′-deoxyuridine. https://app.cochat.ai/papers/10.1093/nar/22.14.2817
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- Latham, J. A., Johnson, R., & Toole, J. J. (1994). The application of a modified nucleotide in aptamer selection: novel thrombin aptamers containing -(1 -pentynyl)-2′-deoxyuridine. Nucleic Acids Research. https://doi.org/10.1093/nar/22.14.2817
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