Kawasaki Takayasu, Onodera Kenji, Kamijo Shunsuke
The University of Tokyo, Institute of Industrial Science, Japan.
Biosci Biotechnol Biochem. 2010;74(11):2214-9. doi: 10.1271/bbb.100388. Epub 2010 Nov 7.
There have been many reports suggesting that soluble oligomers of amyloid β (Aβ) are neurotoxins causing Alzheimer's disease (AD). Although inhibition of the soluble oligomerization of Aβ is considered to be effective in the treatment of AD, almost all peptide inhibitors have been designed from the β-sheet structure (H14-D23) of Aβ(1-42). To obtain more potent peptides than the known inhibitors of the soluble-oligomer formation of Aβ(1-42), we performed random screening by phage display. After fifth-round panning of a hepta-peptide library against soluble Aβ(1-42), novel peptides containing arginine residues were enriched. These peptides were found to suppress specifically 37/48 kDa oligomer formation and to keep the monomeric form of Aβ(1-42) even after 24 h of incubation, as disclosed by SDS-PAGE and size-exclusion chromatography. Thus we succeeded in acquiring novel efficient peptides for inhibition of soluble 37/48 kDa oligomer formation of Aβ(1-42).
有许多报告表明，β淀粉样蛋白（Aβ）的可溶性寡聚体是导致阿尔茨海默病（AD）的神经毒素。尽管抑制Aβ的可溶性寡聚化被认为对AD治疗有效，但几乎所有的肽类抑制剂都是基于Aβ（1-42）的β折叠结构（H14-D23）设计的。为了获得比已知的Aβ（1-42）可溶性寡聚体形成抑制剂更有效的肽，我们通过噬菌体展示进行了随机筛选。用七肽文库对可溶性Aβ（1-42）进行五轮淘选后，富含了含精氨酸残基的新型肽。如SDS-PAGE和尺寸排阻色谱所示，这些肽被发现能特异性抑制37/48 kDa寡聚体的形成，并且即使在孵育24小时后仍能保持Aβ（1-42）的单体形式。因此，我们成功获得了用于抑制Aβ（1-42）可溶性37/48 kDa寡聚体形成的新型高效肽。
