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Structure-Based Optimization of Inhibitors of the Aspartic Protease Endothiapepsin.

Hartman AM, Mondal M, Radeva N, Klebe G, Hirsch AK - Int J Mol Sci (2015)

Bottom Line: 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 Article: PubMed Central - PubMed

Affiliation: Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands. a.m.hartman@student.rug.nl.

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.

No MeSH data available.


Related in: MedlinePlus

Structure of (S)-2-amino-3-(1H-indol-3-yl)propanehydrazide 10.
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ijms-16-19184-f006: Structure of (S)-2-amino-3-(1H-indol-3-yl)propanehydrazide 10.


Structure-Based Optimization of Inhibitors of the Aspartic Protease Endothiapepsin.

Hartman AM, Mondal M, Radeva N, Klebe G, Hirsch AK - Int J Mol Sci (2015)

Structure of (S)-2-amino-3-(1H-indol-3-yl)propanehydrazide 10.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581293&req=5

ijms-16-19184-f006: Structure of (S)-2-amino-3-(1H-indol-3-yl)propanehydrazide 10.
Bottom Line: 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 Article: PubMed Central - PubMed

Affiliation: Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands. a.m.hartman@student.rug.nl.

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.

No MeSH data available.


Related in: MedlinePlus