Structural highlights
Publication Abstract from PubMed
The structure-based design, synthesis, and X-ray structure of protein-ligand complexes of exceptionally potent and selective beta-secretase inhibitors are described. The inhibitors are designed specifically to interact with S(1)' active site residues to provide selectivity over memapsin 1 and cathepsin D. Inhibitor 5 has exhibited exceedingly potent inhibitory activity (K(i) = 17 pM) and high selectivity over BACE 2 (>7000-fold) and cathepsin D (>250000-fold). A protein-ligand crystal structure revealed important molecular insight into these selectivities. These interactions may serve as an important guide to design selectivity over the physiologically important aspartic acid proteases.
Structure-Based Design of Highly Selective beta-Secretase Inhibitors: Synthesis, Biological Evaluation, and Protein-Ligand X-ray Crystal Structure.,Ghosh AK, Venkateswara Rao K, Yadav ND, Anderson DD, Gavande N, Huang X, Terzyan S, Tang J J Med Chem. 2012 Sep 6. PMID:22954357[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ghosh AK, Venkateswara Rao K, Yadav ND, Anderson DD, Gavande N, Huang X, Terzyan S, Tang J. Structure-Based Design of Highly Selective beta-Secretase Inhibitors: Synthesis, Biological Evaluation, and Protein-Ligand X-ray Crystal Structure. J Med Chem. 2012 Sep 6. PMID:22954357 doi:10.1021/jm3008823
