Efficacy of Base-Modification on Target Binding of Small Molecule DNA Aptamers
2013
Imaizumi, Yuri | Kasahara, Yuuya | Fujita, Hiroto | Kitadume, Shunsuke | Ozaki, Hiroaki | Endoh, Tamaki | Kuwahara, Masayasu | Sugimoto, N. (Naoki)
Nucleic acid aptamers are receptors of single-stranded oligonucleotides that specifically bind to their targets. Significant interest is currently focused on development of small molecule aptamers owing to their applications in biosensing, diagnostics, and therapeutics involving low molecular weight biomarkers and drugs. Despite great potential for their diverse applications, relatively few aptamers that bind to small molecules have been reported, and methodologies to enhance and broaden their functions by expanding chemical repertories have barely been examined. Here we describe construction of a modified DNA library that includes (E)-5-(2-(N-(2-(N⁶-adeninyl)ethyl))carbamylvinyl)-uracil bases and discovery of high-affinity camptothecin-binding DNA aptamers using a systematic evolution of ligands by the exponential enrichment method. Our results are the first to demonstrate the superior efficacy of base modification on affinity enhancement and the usefulness of unnatural nucleic acid libraries for development of small molecule aptamers.
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