Inhibition of BACE, a Promising Approach to Alzheimer's Disease Therapy

Author: Roggo, S.

Source: Current Topics in Medicinal Chemistry, Volume 2, Number 4, 1 April 2002 , pp. 359-370(12)

Publisher: Bentham Science Publishers

Key:
Free Content - Free Content
New Content - New Content
Subscribed Content - Subscribed Content
Free Trial Content - Free Trial Content

Abstract:

The first proteolytic step in the processing of amyloid precursor protein (APP) to amyloid-beta (Abgr) in the brain is performed by bgr-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 bgr-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.

Keywords: bace; aspartic protease; inhibition; app; amyliod; pepstatin; protease; indinavir; amprenavir; tipranavir; aliskiren

Document Type: Review article

DOI: 10.2174/1568026024607490

The full text electronic article is available for purchase. You will be able to download the full text electronic article after payment.

$55.10 plus tax      Refund Policy

 

OR

Back to top

Key:
Free Content - Free Content
New Content - New Content
Subscribed Content - Subscribed Content
Free Trial Content - Free Trial Content
Share this item with others: These icons link to social bookmarking sites where readers can share and discover new web pages.
Page Help Click here for Page Help
Shopping cart
Tools
Sign in






Need to register?
Sign up here
Text size: A | A | A | A