A new class of aggregation inhibitor of amyloid-¦Â peptide based on an O-acyl isopeptide

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• 作者：Hiroyuki Kawashima ; Youhei Sohma ; Tomoya Nakanishi ; Hitomi Kitamura ; Hidehito Mukai ; Masayuki Yamashita ; Kenichi Akaji ; Yoshiaki Kiso
• 关键词：A¦Â ; amyloid ¦Â peptide ; AD ; Alzheimer&rsquo ; s disease ; DIC ; N ; N&prime ; -diisopropylcarbodiimide ; DMF ; N ; N-dimethylformamide ; DMSO ; dimethyl sulfoxide ; FAM ; carboxyfluorescein ; HOBt ; N-hydroxybenzotriazole ; HPLC ; high-performance liquid chromatography ; kDa
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2013
• 出版时间：1 November, 2013
• 年：2013
• 卷：21
• 期：21
• 页码：6323-6327
• 全文大小：1770 K

文摘

Inhibition of amyloid ¦Â peptide (A¦Â) aggregation is a potential therapeutic approach to treat Alzheimer¡¯s disease. We report that an O-acyl isopeptide of A¦Â1-42 (1) containing an ester bond at the Gly²⁵-Ser²⁶ moiety inhibits A¦Â1-42 fibril formation at equimolar ratio. Inhibitory activity was retained by an N-Me-¦Â-Ala²⁶ derivative (2), in which the ester of 1 was replaced with N-methyl amide to improve chemical stability at physiological pH. Inhibition was verified by fluorescence anisotropy, Western blot, and atomic force microscopy. This report suggests a new class of A¦Â aggregation inhibitor based on modification of A¦Â1-42 at Gly²⁵-Ser²⁶.