Structure-Based Optimization of Inhibitors of the Aspartic Protease EndothiapepsinHartman, A. M., Mondal, M., Radeva, N., Klebe, G. & Hirsch, A. K. H., 14-Aug-2015, In : International Journal of Molecular Sciences. 16, 8, p. 19184-94 11 p.
Research output: Contribution to journal › Article › Academic › peer-review
Aspartic proteases are a class of enzymes that play a causative role in numerous diseases such as malaria (plasmepsins), Alzheimer's disease (β-secretase), fungal infections (secreted aspartic proteases), and hypertension (renin). We have chosen endothiapepsin as a model enzyme of this class of enzymes, for the design, preparation and biochemical evaluation of a new series of inhibitors of endothiapepsin. Here, we have optimized a hit, identified by de novo structure-based drug design (SBDD) and DCC, by using structure-based design approaches focusing on the optimization of an amide-π interaction. Biochemical results are in agreement with SBDD. These results will provide useful insights for future structure-based optimization of inhibitors for the real drug targets as well as insights into molecular recognition.
|Number of pages||11|
|Journal||International Journal of Molecular Sciences|
|Publication status||Published - 14-Aug-2015|
- HYDE SCORING FUNCTION, X-RAY, MEDICINAL CHEMISTRY, CATALYTIC MECHANISM, DRUG DESIGN, NEUTRON, PROTEINASES, DIFFRACTION, DISCOVERY, structure based drug design, INHIBITORS, aspartic protease endothiapepsin, molecular recognition