Next Article in Journal
Gene Networks Involved in Hormonal Control of Root Development in Arabidopsis thaliana: A Framework for Studying Its Disturbance by Metal Stress
Next Article in Special Issue
Resolving Intra- and Inter-Molecular Structure with Non-Contact Atomic Force Microscopy
Previous Article in Journal
Cdc42-Interacting Protein 4 Represses E-Cadherin Expression by Promoting β-Catenin Translocation to the Nucleus in Murine Renal Tubular Epithelial Cells
Previous Article in Special Issue
Generation of a Multicomponent Library of Disulfide Donor-Acceptor Architectures Using Dynamic Combinatorial Chemistry
Article Menu
Issue 8 (August) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2015, 16(8), 19184-19194;

Structure-Based Optimization of Inhibitors of the Aspartic Protease Endothiapepsin

Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands
Institute of Pharmaceutical Chemistry, Philipps-University Marburg, Marbacher Weg 6, 35032 Marburg, Germany
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: John George Hardy
Received: 1 May 2015 / Revised: 27 June 2015 / Accepted: 6 July 2015 / Published: 14 August 2015
(This article belongs to the Special Issue Supramolecular Interactions)
Full-Text   |   PDF [1488 KB, uploaded 14 August 2015]   |  


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. View Full-Text
Keywords: inhibitors; aspartic protease endothiapepsin; structure-based drug design; molecular recognition inhibitors; aspartic protease endothiapepsin; structure-based drug design; molecular recognition

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

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.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top