title: Improvement of Aptamer Affinity by Dimerization.
abstract: To increase the affinities of aptamers for their targets, we designed an aptamerdimer for thrombin and VEGF. This design is based on the avidity of the antibody, whichenables the aptamer to connect easily since it is a single-strand nucleic acid. In this study,we connected a 15-mer thrombin-binding aptamer with a 29-mer thrombin-binding aptamer.Each aptamer recognizes a different part of the thrombin molecule, and the aptamer dimerhas a Kdvalue which is 1/10 of that of the monomers from which it is composed. Also, thedesigned aptamer dimer has higher inhibitory activity than the reported (15-mer) thrombin-inhibiting aptamer. Additionally, we connected together two identical aptamers againstvascular endothelial growth factor (VEGF165), which is a homodimeric protein. As in thecase of the anti-thrombin aptamer, the dimeric anti-VEGF aptamer had a much lower Kdvalue than that of the monomer. This study demonstrated that the dimerization of aptamerseffectively improves the affinities of those aptamers for their targets.
authors.affiliation: Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan.
authors.forename: Hijiri
authors.initials: H
authors.lastname: Hasegawa
authors.affiliation: Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Taira
authors.affiliation: Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan. sode@cc.tuat.ac.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Sode
authors.affiliation: Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan. ikebu@cc.tuat.ac.jp.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ikebukuro
keywords: Aptamer; avidity; dimerization