Structural highlights
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Structure-based design and synthesis of novel P2/P3 modified, non-peptidic beta-secretase (BACE-1) inhibitors.,Hanessian S, Shao Z, Betschart C, Rondeau JM, Neumann U, Tintelnot-Blomley M Bioorg Med Chem Lett. 2010 Mar 15;20(6):1924-7. Epub 2010 Feb 2. PMID:20172717[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hanessian S, Shao Z, Betschart C, Rondeau JM, Neumann U, Tintelnot-Blomley M. Structure-based design and synthesis of novel P2/P3 modified, non-peptidic beta-secretase (BACE-1) inhibitors. Bioorg Med Chem Lett. 2010 Mar 15;20(6):1924-7. Epub 2010 Feb 2. PMID:20172717 doi:10.1016/j.bmcl.2010.01.139
