Structure-Based Design and Synthesis of Macroheterocyclic Peptidomimetic Inhibitors of the Aspartic Protease β-Site Amyloid Precursor Protein Cleaving Enzyme (BACE)

2006 ◽  
Vol 49 (15) ◽  
pp. 4544-4567 ◽  
Author(s):  
Stephen Hanessian ◽  
Gaoqiang Yang ◽  
Jean-Michel Rondeau ◽  
Ulf Neumann ◽  
Claudia Betschart ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Aspartic Protease ◽  
Precursor Protein ◽  
Design And Synthesis ◽  
Peptidomimetic Inhibitors

Memapsin 2, a drug target for Alzheimer's disease

2003 ◽  
Vol 70 ◽  
pp. 213-220 ◽  
Author(s):  
Gerald Koelsch ◽  
Robert T. Turner ◽  
Lin Hong ◽  
Arun K. Ghosh ◽  
Jordan Tang
Keyword(s):  
Crystal Structure ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transition State ◽  
Amyloid Precursor Protein ◽  
Therapeutic Target ◽  
Drug Target ◽  
Aspartic Protease ◽  
Precursor Protein ◽  
Memapsin 2

Mempasin 2, a ϐ-secretase, is the membrane-anchored aspartic protease that initiates the cleavage of amyloid precursor protein leading to the production of ϐ-amyloid and the onset of Alzheimer's disease. Thus memapsin 2 is a major therapeutic target for the development of inhibitor drugs for the disease. Many biochemical tools, such as the specificity and crystal structure, have been established and have led to the design of potent and relatively small transition-state inhibitors. Although developing a clinically viable mempasin 2 inhibitor remains challenging, progress to date renders hope that memapsin 2 inhibitors may ultimately be useful for therapeutic reduction of ϐ-amyloid.

scholarly journals Human aspartic protease memapsin 2 cleaves the beta -secretase site of beta -amyloid precursor protein

2000 ◽  
Vol 97 (4) ◽  
pp. 1456-1460 ◽  
Author(s):  
X. Lin ◽  
G. Koelsch ◽  
S. Wu ◽  
D. Downs ◽  
A. Dashti ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Beta Amyloid ◽  
Aspartic Protease ◽  
Precursor Protein ◽  
Beta Secretase ◽  
Memapsin 2

Design and Synthesis of β-Site Amyloid Precursor Protein Cleaving Enzyme (BACE1) Inhibitors with in Vivo Brain Reduction of β-Amyloid Peptides

2012 ◽  
Vol 55 (21) ◽  
pp. 9346-9361 ◽  
Author(s):  
Britt-Marie Swahn ◽  
Karin Kolmodin ◽  
Sofia Karlström ◽  
Stefan von Berg ◽  
Peter Söderman ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Amyloid Peptides ◽  
Design And Synthesis ◽  
Β Amyloid

Design and Synthesis of Clinical Candidate PF-06751979: A Potent, Brain Penetrant, β-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) Inhibitor Lacking Hypopigmentation

2018 ◽  
Vol 61 (10) ◽  
pp. 4476-4504 ◽  
Author(s):  
Brian T. O’Neill ◽  
Elizabeth M. Beck ◽  
Christopher R. Butler ◽  
Charles E. Nolan ◽  
Cathleen Gonzales ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Bace1 Inhibitor ◽  
Design And Synthesis ◽  
Clinical Candidate

Structural Features of Human Memapsin 2 (β-Secretase) and their Biological and Pathological Implications

2004 ◽  
Vol 36 (12) ◽  
pp. 787-792 ◽  
Author(s):  
Lin Hong ◽  
Xiangyuan He ◽  
Xiangping Huang ◽  
Wanpin Chang ◽  
Jordan Tang
Keyword(s):  
Amyloid Precursor Protein ◽  
Transmembrane Domain ◽  
Amyloid Β ◽  
Structural Features ◽  
Aspartic Protease ◽  
Precursor Protein ◽  
The Past ◽  
Memapsin 2 ◽  
Β Amyloid ◽  
Major Target

Abstract Memapsin 2 (β-secretase) is the membrane-anchored aspartic protease that initiates the cleavage of β-amyloid precursor protein (APP) leading to the production of amyloid-β (Aβ), a major factor in the pathogenesis of Alzheimer's disease (AD). Since memapsin 2 is a major target for the development of inhibitor drugs for AD, it has been intensively studied during the past five years. Here we discuss the structural features of the catalytic/specificity apparatus, transmembrane domain, cytosolic domain and the implications of these features in the physiological and pathological roles of this protease.

Design and Synthesis of Potent, Orally Efficacious Hydroxyethylamine Derived β-Site Amyloid Precursor Protein Cleaving Enzyme (BACE1) Inhibitors

2012 ◽  
Vol 55 (21) ◽  
pp. 9025-9044 ◽  
Author(s):  
Thomas A. Dineen ◽  
Matthew M. Weiss ◽  
Toni Williamson ◽  
Paul Acton ◽  
Safura Babu-Khan ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Precursor Protein ◽  
Design And Synthesis

Interplay between Pur α and Egr-1 in the transcriptional regulation of amyloid precursor protein gene expression

2010 ◽  
Vol 34 (8) ◽  
pp. S27-S27
Author(s):  
Jianqi Cui ◽  
Xiuying Pei ◽  
Qian Zhang ◽  
Bassel E. Sawaya ◽  
Xiaohong Lu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Amyloid Precursor Protein ◽  
Protein Gene ◽  
Precursor Protein ◽  
Amyloid Precursor Protein Gene

Insulinrezeptorsubstrat (IRS)2-Expression moduliert die Amyloid-Precursor-Protein (APP) Spaltung in vivo

2010 ◽  
Vol 5 (S 01) ◽  
Author(s):  
M Udelhoven ◽  
T Ehlkes ◽  
MM Hettich ◽  
S Asrat ◽  
W Krone ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Precursor Protein
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