Structure-Based Optimization of Inhibitors of the Aspartic Protease Endothiapepsin
AbstractAspartic 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. View Full-Text
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Hartman, A.M.; Mondal, M.; Radeva, N.; Klebe, G.; Hirsch, A.K.H. Structure-Based Optimization of Inhibitors of the Aspartic Protease Endothiapepsin. Int. J. Mol. Sci. 2015, 16, 19184-19194.
Hartman AM, Mondal M, Radeva N, Klebe G, Hirsch AKH. Structure-Based Optimization of Inhibitors of the Aspartic Protease Endothiapepsin. International Journal of Molecular Sciences. 2015; 16(8):19184-19194.Chicago/Turabian Style
Hartman, Alwin M.; Mondal, Milon; Radeva, Nedyalka; Klebe, Gerhard; Hirsch, Anna K.H. 2015. "Structure-Based Optimization of Inhibitors of the Aspartic Protease Endothiapepsin." Int. J. Mol. Sci. 16, no. 8: 19184-19194.