‘Click peptide’ using production of monomer Aβ from the O-acyl isopeptide: Application to assay system of aggregation inhibitors and cellular cytotoxicity

详细信息    查看全文

• 作者：Youhei Sohma ; ^a ; ^{ysohma@mb.kyoto-phu.ac.jp} ; Yuta Hirayama^a ; Atsuhiko Taniguchi^a ; Hidehito Mukai^a ; Yoshiaki Kiso ; ^a ; ^{kiso@mb.kyoto-phu.ac.jp}
• 关键词：Aggregation ; Amyloid ; Alzheimer ; Click peptide ; Inhibitor ; Isopeptide
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2011
• 出版时间：1 March 2011
• 年：2011
• 卷：19
• 期：5
• 页码：1729-1733
• 全文大小：534 K

文摘

The O-acyl isopeptide of Aβ1–42 (1), possessing an ester bond at the Gly²⁵-Ser²⁶ sequence, is a water-soluble and non-aggregative precursor molecule and is capable of production of monomer Aβ1–42. The SDS–PAGE result showed that the Aβ1–42, produced from 1, adopted monomeric state at first and then self-assembled to oligomer. The oligomeric state was stabilized by nordihydroguaiaretic acid. The Thioflavin-T (ThT) fluorescence intensity derived from Aβ1–42 (generated from 1) was suppressed by various aggregation inhibitors. Finally, 1 could generate Aβ1–42 via the O-to-N acyl migration under cellular medium conditions and the produced Aβ1–42 exhibited cytotoxicity against PC12 cells. These results suggest that the click peptide system, which enables us to predominantly produce monomer Aβ1–42 under physiological conditions, would be adoptable to various biochemical and biophysical experiments including cellular system to investigate the functions of Aβ1–42.