| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1371937 | Bioorganic & Medicinal Chemistry Letters | 2010 | 4 Pages |
Abstract
Starting from peptidomimetic BACE-1 inhibitors, the P2 amino acid including the P2/P3 peptide bond was replaced by a rigid 3-aminomethyl cyclohexane carboxylic acid. Co-crystallization revealed an unexpected binding mode with the P3/P4 amide bond placed into the S3 pocket resulting in a new hydrogen bond interaction pattern. Further optimization based on this structure resulted in highly potent BACE-1 inhibitors with selectivity over BACE-2 and cathepsin D.
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Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Stephen Hanessian, Zhihui Shao, Claudia Betschart, Jean-Michel Rondeau, Ulf Neumann, Marina Tintelnot-Blomley,