We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Structure-Based Optimization of Inhibitors of the Aspartic Protease Endothiapepsin.
- Authors
Hartman, Alwin M.; Mondal, Milon; Radeva, Nedyalka; Klebe, Gerhard; Hirsch, Anna K. H.
- Abstract
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.
- Subjects
ENDOTHIAPEPSIN; ENDOPEPTIDASES; PEPTIDASE; SIGNAL peptidases; PROTEOLYTIC enzymes
- Publication
International Journal of Molecular Sciences, 2015, Vol 16, Issue 8, p19184
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms160819184