title: Novel high-affinity Aβ-binding peptides identified by an advanced in vitro evolution, progressive library method.
abstract: Recent studies have been supporting that the generation of Aβ42 oligomers is responsible for Alzheimer's disease. Therefore, those peptides which bind to Aβ42 are scientifically interesting and can be possible candidates for the diagnosis and therapy of Alzheimer's disease. A systemic in vitro evolution, developed recently and the designated progressive library method (PLM), was applied to obtain Ab42-binding aptamers peptides. As a result, high affinity peptide aptamers made of 8 or 9 amino acids could be identified by this approach, endorsing the methodological effectiveness. Namely, the selection products from the secondary library of diversified peptides, which was constructed based on the information obtained from the primary library selection, were confirmed to be superior to those selected from the primary library as had been reported previously. The affinities of those peptides measured by SPR (surface plasmon resonance) were comparable to or higher than that of those peptides so far reported (K(d) of 10⁻⁷). The other peptides selected were confirmed of their binding by a novel mode of gel shift assay (fluorescence enhancement caused by the binding). Thus, novel Aβ42-binding peptides with high affinity were provided for the future Alzheimer's disease study. The demonstration of the effectiveness of the systemic in vitro evolution of PLM is very encouraging for the study of identifying novel functional peptides.
authors.affiliation: Department of Functional Materials Science, Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, Japan.
authors.forename: Sachika
authors.initials: S
authors.lastname: Tsuji-Ueno
authors.forename: Masayuki
authors.initials: M
authors.lastname: Komatsu
authors.forename: Kakeru
authors.initials: K
authors.lastname: Iguchi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takahashi
authors.forename: Syuhei
authors.initials: S
authors.lastname: Yoshino
authors.forename: Miho
authors.initials: M
authors.lastname: Suzuki
authors.forename: Naoto
authors.initials: N
authors.lastname: Nemoto
authors.forename: Koichi
authors.initials: K
authors.lastname: Nishigaki
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D052158:Aptamers, Peptide / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D019020:Directed Molecular Evolution / Q000379:methods*; D010446:Peptide Fragments / Q000378:metabolism*; D019151:Peptide Library; D011485:Protein Binding
chemical_list: D016229:Amyloid beta-Peptides; D052158:Aptamers, Peptide; D010446:Peptide Fragments; D019151:Peptide Library; C075222:amyloid beta-protein (1-42)