Kawasaki Takayasu, Onodera Kenji, Kamijo Shunsuke
Institute of Industrial Science, The University of Tokyo, Meguro-ku, Tokyo, Japan.
Biosci Biotechnol Biochem. 2011;75(8):1496-501. doi: 10.1271/bbb.110198. Epub 2011 Aug 7.
Since the soluble oligomers of 42-residue amyloid β (Aβ42) might be neurotoxins at an early stage of Alzheimer's disease (AD), inhibition of soluble Aβ42 oligomerization should be effective in the treatment of AD. We have found by phage display that a 7-residue peptide, SRPGLRR, exhibited inhibitory activity against soluble 37/48 kDa oligomers of Aβ42. In the present study, we newly prepared 3- and 4-residue random peptides libraries and performed pannings of them against soluble Aβ42 to search for important factors in the inhibition of Aβ42 oligomerization. After the fifth round, arginine-containing peptides were enriched in both libraries. SDS-PAGE and size-exclusion chromatography indicated that the inhibitory activities of 4-residue peptides against the soluble 37/48 kDa oligomers of Aβ42 were higher than those of the 3-residue peptides, and RFRK exhibited strong inhibitory activity as well as SRPGLRR. These short peptides should be useful for the suppression of soluble Aβ42 oligomer formation.
由于42个氨基酸残基的淀粉样β蛋白（Aβ42）的可溶性寡聚体可能是阿尔茨海默病（AD）早期的神经毒素，抑制可溶性Aβ42寡聚化在AD治疗中应是有效的。我们通过噬菌体展示发现，一个7个氨基酸残基的肽SRPGLRR对Aβ42的可溶性37/48 kDa寡聚体具有抑制活性。在本研究中，我们新制备了3个和4个氨基酸残基的随机肽库，并针对可溶性Aβ42对它们进行淘选，以寻找抑制Aβ42寡聚化的重要因素。在第五轮之后，两个库中富含含精氨酸的肽。SDS-PAGE和尺寸排阻色谱表明，4个氨基酸残基的肽对Aβ42可溶性37/48 kDa寡聚体的抑制活性高于3个氨基酸残基的肽，并且RFRK与SRPGLRR一样表现出很强的抑制活性。这些短肽应有助于抑制可溶性Aβ42寡聚体的形成。
