Novel High-affinity A beta-binding Peptides Identified by an Advanced In Vitro Evolution, Progressive Library Method

作者：Tsuji Ueno Sachika; Komatsu Masayuki; Iguchi Kakeru; Takahashi Masahiro; Yoshino Syuhei; Suzuki Miho; Nemoto Naoto; Nishigaki Koichi^*

来源：Protein and Peptide Letters, 2011, 18(6): 642-650.

DOI：10.2174/092986611795222678

• Alzheimer's disease
• amyloid beta
• cDNA display
• in vitro evolution
• peptide aptamer
• progressive library method

Recent studies have been supporting that the generation of A 42 oligomers is responsible for Alzheimer's disease. Therefore, those peptides which bind to A 42 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 A beta 42-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 A beta 42-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.

• 出版日期2011-6