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Inhibition of BACE, a promising approach to Alzheimer's disease therapy

Roggo, Silvio (2002) Inhibition of BACE, a promising approach to Alzheimer's disease therapy. Current Topics in Medicinal Chemistry, 2 (4). pp. 359-370. ISSN 1568-0266


The first proteolytic step in the processing of amyloid precursor protein (APP) to amyloid-beta (Abeta) in the brain is performed by beta-site APP cleaving enzyme (BACE1). This enzyme is a membrane bound aspartic protease with high homology of the catalytic domain to renin and pepsin and of yet unknown physiologic function. It is a primary drug discovery target for Alzheimer s disease therapy. The first potent inhibitors are based on the sequence of APP around the beta-secretase cleavage site EVNL/DAEF, with the scissile Leu-Asp amide bond being replaced by a hydroxyethylene transition state analogue isostere. In addition, lipophilic sidechains have been incorporated and a crystal structure of such an octapeptidic inhibitor bound in the active site is already available. Recent progress in the field of BACE inhibition is reviewed.

Item Type: Article
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Additional Information: Author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords: bace; aspartic protease; inhibition; app; amyliod; pepstatin; protease; indinavir; amprenavir; tipranavir; aliskiren
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Date Deposited: 29 Apr 2010 23:45
Last Modified: 01 Feb 2013 00:49


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