Selection of DNA aptamers with two modified bases.
In: Proceedings of the National Academy of Sciences of the United States of America, Jg. 114 (2017-03-14), Heft 11, S. 2898
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Zugriff:
The nucleobases comprising DNA and RNA aptamers provide considerably less chemical diversity than protein-based ligands, limiting their versatility. The introduction of novel functional groups at just one of the four bases in modified aptamers has recently led to dramatic improvement in the success rate of identifying nucleic acid ligands to protein targets. Here we explore the benefits of additional enhancement in physicochemical diversity by selecting modified DNA aptamers that contain amino-acid-like modifications on both pyrimidine bases. Using proprotein convertase subtilisin/kexin type 9 as a representative protein target, we identify specific pairwise combinations of modifications that result in higher affinity, metabolic stability, and inhibitory potency compared with aptamers with single modifications. Such doubly modified aptamers are also more likely to be encoded in shorter sequences and occupy nonoverlapping epitopes more frequently than aptamers with single modifications. These highly modified DNA aptamers have broad utility in research, diagnostic, and therapeutic applications.
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Selection of DNA aptamers with two modified bases.
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Autor/in / Beteiligte Person: | Gawande, BN ; Rohloff, JC ; Carter, JD ; von Carlowitz I ; Zhang, C ; Schneider, DJ ; Janjic, N |
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Zeitschrift: | Proceedings of the National Academy of Sciences of the United States of America, Jg. 114 (2017-03-14), Heft 11, S. 2898 |
Veröffentlichung: | Washington, DC : National Academy of Sciences, 2017 |
Medientyp: | academicJournal |
ISSN: | 1091-6490 (electronic) |
DOI: | 10.1073/pnas.1615475114 |
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