
Fragment-Based De Novo Design Reveals a Small-Molecule Inhibitor of Helicobacter Pylori HtrA.
Publication
, Journal Article
Perna, AM; Rodrigues, T; Schmidt, TP; Böhm, M; Stutz, K; Reker, D; Pfeiffer, B; Altmann, K-H; Backert, S; Wessler, S; Schneider, G
Published in: Angewandte Chemie (International ed. in English)
August 2015
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.
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Published In
Angewandte Chemie (International ed. in English)
DOI
EISSN
1521-3773
ISSN
1433-7851
Publication Date
August 2015
Volume
54
Issue
35
Start / End Page
10244 / 10248
Related Subject Headings
- Structure-Activity Relationship
- Small Molecule Libraries
- Protease Inhibitors
- Peptide Hydrolases
- Organic Chemistry
- Ligands
- Humans
- Helicobacter pylori
- Helicobacter Infections
- Drug Discovery
Citation
APA
Chicago
ICMJE
MLA
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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 Ed. in English), 54(35), 10244–10248. https://doi.org/10.1002/anie.201504035
Perna, Anna M., Tiago Rodrigues, Thomas P. Schmidt, Manja Böhm, Katharina Stutz, Daniel Reker, Bernhard Pfeiffer, et al. “Fragment-Based De Novo Design Reveals a Small-Molecule Inhibitor of Helicobacter Pylori HtrA.” Angewandte Chemie (International Ed. in English) 54, no. 35 (August 2015): 10244–48. https://doi.org/10.1002/anie.201504035.
Perna AM, Rodrigues T, Schmidt TP, Böhm M, Stutz K, Reker D, et al. Fragment-Based De Novo Design Reveals a Small-Molecule Inhibitor of Helicobacter Pylori HtrA. Angewandte Chemie (International ed in English). 2015 Aug;54(35):10244–8.
Perna, Anna M., et al. “Fragment-Based De Novo Design Reveals a Small-Molecule Inhibitor of Helicobacter Pylori HtrA.” Angewandte Chemie (International Ed. in English), vol. 54, no. 35, Aug. 2015, pp. 10244–48. Epmc, doi:10.1002/anie.201504035.
Perna AM, Rodrigues T, Schmidt TP, Böhm M, Stutz K, Reker D, Pfeiffer B, Altmann K-H, Backert S, Wessler S, Schneider G. Fragment-Based De Novo Design Reveals a Small-Molecule Inhibitor of Helicobacter Pylori HtrA. Angewandte Chemie (International ed in English). 2015 Aug;54(35):10244–10248.

Published In
Angewandte Chemie (International ed. in English)
DOI
EISSN
1521-3773
ISSN
1433-7851
Publication Date
August 2015
Volume
54
Issue
35
Start / End Page
10244 / 10248
Related Subject Headings
- Structure-Activity Relationship
- Small Molecule Libraries
- Protease Inhibitors
- Peptide Hydrolases
- Organic Chemistry
- Ligands
- Humans
- Helicobacter pylori
- Helicobacter Infections
- Drug Discovery