Monitoring β-Secretase Activity in Living Cells with a Membrane-Anchored FRET Probe

被引:29
作者
Folk, Drew S. [1 ]
Torosian, Justin C. [1 ]
Hwang, Sunhee [1 ]
McCafferty, Dewey G. [1 ]
Franz, Katherine J. [1 ]
机构
[1] Duke Univ, Dept Chem, Durham, NC 27708 USA
基金
美国国家卫生研究院;
关键词
Alzheimer's disease; analytical methods; enzymes; Forster resonance energy transfer (FRET); imaging agents; AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; POTENT INHIBITORS; BACE-1; INHIBITORS; ALPHA-SECRETASE; LIPID RAFTS; IN-VITRO; DESIGN; OLIGOMERIZATION; CLEAVAGE;
D O I
10.1002/anie.201206673
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Turn it on! β-MAP is a sensitive FRET probe with specificity for monitoring the enzyme β-secretase (BACE), which is associated with Alzheimer's disease. After hydrolysis by the enzyme BACE, the probe fluoresces and thus allows real-time spatial and temporal assessment of enzymatic activity in living cells. β-MAP was used to confirm the cellular efficacy of a reported inhibitor without the need for mutated cell lines or antibodies. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
引用
收藏
页码:10795 / 10799
页数:5
相关论文
共 35 条
[1]   BACE1- and BACE2-expressing human cells -: Characterization of β-amyloid precursor protein-derived catabolites, design of a novel fluorimetric assay, and identification of new in vitro inhibitors [J].
Andrau, D ;
Dumanchin-Njock, C ;
Ayral, E ;
Vizzavona, J ;
Farzan, M ;
Boisbrun, M ;
Fulcrand, P ;
Hernandez, JF ;
Martinez, J ;
Lefranc-Jullien, S ;
Checler, F .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (28) :25859-25866
[2]   From Fragment Screening to In Vivo Efficacy: Optimization of a Series of 2-Aminoquinolines as Potent Inhibitors of Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) [J].
Cheng, Yuan ;
Judd, Ted C. ;
Bartberger, Michael D. ;
Brown, James ;
Chen, Kui ;
Fremeau, Robert T., Jr. ;
Hickman, Dean ;
Hitchcock, Stephen A. ;
Jordan, Brad ;
Li, Vivian ;
Lopez, Patricia ;
Louie, Steven W. ;
Luo, Yi ;
Michelsen, Klaus ;
Nixey, Thomas ;
Powers, Timothy S. ;
Rattan, Claire ;
Sickmier, E. Allen ;
St Jean, David J. ;
Wahl, Robert C. ;
Wen, Paul H. ;
Wood, Stephen .
JOURNAL OF MEDICINAL CHEMISTRY, 2011, 54 (16) :5836-5857
[3]   Membrane-bound FRET probe visualizes MMP12 activity in pulmonary inflammation [J].
Cobos-Correa, Amanda ;
Trojanek, Johanna B. ;
Diemer, Stefanie ;
Mall, Marcus A. ;
Schultz, Carsten .
NATURE CHEMICAL BIOLOGY, 2009, 5 (09) :628-630
[4]   Application of fragment screening by X-ray crystallography to the discovery of aminopyridines as inhibitors of β-secretase [J].
Congreve, Miles ;
Aharony, David ;
Albert, Jeffrey ;
Callaghan, Owen ;
Campbell, James ;
Carr, Robin A. E. ;
Chessari, Gianni ;
Cowan, Suzanna ;
Edwards, Philip D. ;
Frederickson, Martyn ;
McMenamin, Rachel ;
Murray, Christopher W. ;
Patel, Sahil ;
Wallis, Nicola .
JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (06) :1124-1132
[5]   Mechanisms of Aβ mediated neurodegeneration in Alzheimer's disease [J].
Crouch, Peter J. ;
Harding, Susan-Marie E. ;
White, Anthony R. ;
Camakaris, James ;
Bush, Ashley I. ;
Masters, Colin L. .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2008, 40 (02) :181-198
[6]   Upregulation of the α-secretase ADAM10-risk or reason for hope? [J].
Endres, Kristina ;
Fahrenholz, Falk .
FEBS JOURNAL, 2010, 277 (07) :1585-1596
[7]   Proteolytic activation of recombinant pro-memapsin 2 (pro-β-secretase) studied with new fluorogenic substrates [J].
Ermolieff, J ;
Loy, JA ;
Koelsch, G ;
Tang, J .
BIOCHEMISTRY, 2000, 39 (40) :12450-12456
[8]   BACE: Therapeutic target and potential biomarker for Alzheimer's disease [J].
Evin, Genevieve ;
Barakat, Adel ;
Masters, Colin L. .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2010, 42 (12) :1923-1926
[9]   A Prochelator Activated by β-Secretase Inhibits Aβ Aggregation and Suppresses Copper-Induced Reactive Oxygen Species Formation [J].
Folk, Drew S. ;
Franz, Katherine J. .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2010, 132 (14) :4994-+
[10]   Towards Disease-Modifying Treatment of Alzheimer's Disease: Drugs Targeting β-Amyloid [J].
Frisardi, V. ;
Solfrizzi, V. ;
Imbimbo, B. P. ;
Capurso, C. ;
D'Introno, A. ;
Colacicco, A. M. ;
Vendemiale, G. ;
Seripa, D. ;
Pilotto, A. ;
Capurso, A. ;
Panza, F. .
CURRENT ALZHEIMER RESEARCH, 2010, 7 (01) :40-55