title: Efficacy of base-modification on target binding of small molecule DNA aptamers.
abstract: 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-(N(6)-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.
authors.affiliation: Graduate School of Science and Technology, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Imaizumi
authors.forename: Yuuya
authors.initials: Y
authors.lastname: Kasahara
authors.forename: Hiroto
authors.initials: H
authors.lastname: Fujita
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kitadume
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ozaki
authors.forename: Tamaki
authors.initials: T
authors.lastname: Endoh
authors.forename: Masayasu
authors.initials: M
authors.lastname: Kuwahara
authors.forename: Naoki
authors.initials: N
authors.lastname: Sugimoto
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry*; D001665:Binding Sites; D015394:Molecular Structure; D014498:Uracil / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: C585546:(E)-5-(2-(N-(2-(N6-adeninyl)ethyl))carbamylvinyl)-uracil; D052157:Aptamers, Nucleotide; D014498:Uracil