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β-Secretase as a Therapeutic Target for Inhibitor Drugs

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Recent identification of β-scretasse being a membrane-associated aspartic protease has stimulated strong interest on this enzyme as a therapeutic target for Alzheimer's disease. Here we review the current understanding in the structure-function relationship as well as the status in the design of its inhibitors of this protease, memapsin 2 (BACE, ASP-2). The development in the basic tools, such as the preparation of recombinant memapsin 2, the assay method for kinetic measurements of inhibition, the determination of the subsite specificity and the crystal structure of memapsin 2 complexed to a tight-binding inhibitor, has made the structural based inhibitor design possible. More recent inhibitors, having Ki values in the nanomolar range and molecular size in low 700 Da, show some promise that clinically useful inhibitors of β-scretasse may be attainable.
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Keywords: asp-2; beta secretase; beta secretase and inhibitor; memapsin 2

Document Type: Review Article

Publication date: 2002-06-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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