Fragment-Based de Novo Design Reveals a Small-Molecule Inhibitor of Helicobacter Pylori HtrA

Perna AM, Rodrigues T, Schmidt TP, Böhm M, Stutz K, Reker D, Pfeiffer B, Altmann KH, Backert S, Wessler S, Schneider G (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Angewandte Chemie International Edition Wiley

Book Volume: 54

Pages Range: 10244-10248

Journal Issue: 35

DOI: 10.1002/anie.201504035

Abstract

Sustained identification of innovative chemical entities is key for the success of chemical biology and drug discovery. We report the fragment-based, computer-assisted de novo design of a small molecule inhibiting Helicobacter pylori HtrA protease. Molecular binding of the designed compound to HtrA was confirmed through biophysical methods, supporting its functional activity in vitro. Hit expansion led to the identification of the currently best-in-class HtrA inhibitor. The results obtained reinforce the validity of ligand-based de novo design and binding-kinetics-guided optimization for the efficient discovery of pioneering lead structures and prototyping drug-like chemical probes with tailored bioactivity.

Authors with CRIS profile

Manja Böhm Lehrstuhl für Mikrobiologie Steffen Backert Lehrstuhl für Mikrobiologie

Involved external institutions

École Polytechnique Fédérale de Lausanne (EPFL) CH Switzerland (CH) Universität Salzburg (Paris Lodron Universität Salzburg) AT Austria (AT)

How to cite

APA:

Perna, A.M., Rodrigues, T., Schmidt, T.P., Böhm, M., Stutz, K., Reker, D.,... Schneider, G. (2015). Fragment-Based de Novo Design Reveals a Small-Molecule Inhibitor of Helicobacter Pylori HtrA. Angewandte Chemie International Edition, 54(35), 10244-10248. https://doi.org/10.1002/anie.201504035

MLA:

Perna, Anna M., et al. "Fragment-Based de Novo Design Reveals a Small-Molecule Inhibitor of Helicobacter Pylori HtrA." Angewandte Chemie International Edition 54.35 (2015): 10244-10248.

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