Nonspecificity of Binding of γ-Secretase Modulators to the Amyloid Precursor Protein

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• 作者：Andrew J. Beel ; Paul Barrett ; Paul D. Schnier ; Stephen A. Hitchcock ; Dhanashri Bagal ; Charles R. Sanders ; John B. Jordan
• 刊名：Biochemistry
• 出版年：2009
• 出版时间：December 22, 2009
• 年：2009
• 卷：48
• 期：50
• 页码：11837-11839
• 全文大小：669K
• 年卷期：v.48,no.50(December 22, 2009)
• ISSN：1520-4995

文摘

Evidence that certain γ-secretase modulators (GSMs) target the 99-residue C-terminal domain (C99) of the amyloid precursor protein, a substrate of γ-secretase, but not the protease complex itself has been presented [Kukar, T. L., et al. (2008) Nature 453, 925−929]. Here, NMR results demonstrate a lack of specific binding of these GSMs to monodisperse C99 in LMPG micelles. In addition, results indicate that C99 was likely to have been aggregated in some of the key experiments of the previous work and that binding of GSMs to these C99 aggregates is also of a nonspecific nature.