Volume 6 Supplement 1

9th German Conference on Chemoinformatics

Open Access

Peptide lineup against Gram-negative bacterial infection – first-in-class peptide inhibitor of H. pylori HtrA

  • Anna M Perna1,
  • Thomas Schmidt2,
  • Tim Fugmann3,
  • Nicole Tegtmeyer4,
  • Steffen Backert4,
  • Silja Wessler2 and
  • G Schneider1
Journal of Cheminformatics20146(Suppl 1):P46

https://doi.org/10.1186/1758-2946-6-S1-P46

Published: 11 March 2014

More than 50% of the world population is infected with Helicobacter pylori (H. pylori) and the actual H. pylori treatments fail with increased regularity because of continuously rising antibiotic resistances. To meet this challenge, we focus on the development of a new anti-infective therapy against H. pylori by targeting a secreted enzyme, high temperature requirement A (HtrA). Release of the serine protease HtrA near the host’s gastric epithelial cells leads to loss of cellular adhesion due to E- cadherin cleavage [1]. We investigated the substrate cleavage sites of HtrA in its natural substrate E-cadherin performing a label-free mass spectrometry-based proteomic analysis and identified preferred cleavage positions by Edman sequencing. Further, we developed the first HtrA peptide inhibitor by synthesizing cleavage site fragments and analogues. Surface plasmon resonance (SPR) was used to perform binding studies. In vitro substrate cleavage assays as well as cellular infection assays fully support the biophysical data.

Authors’ Affiliations

(1)
Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH)
(2)
Department of Molecular Biology, University of Salzburg
(3)
Philochem AG
(4)
Department of Biology, University of Erlangen-Nuremberg

References

  1. Hoy B, Löwer M, Weydig C, Carra G, Tegtmeyer N, Geppert T, Schröder P, Sewald N, Backert S, Schneider G, Wessler S: EMBO Rep. 2010, 11: 798-804. 10.1038/embor.2010.114.View ArticleGoogle Scholar

Copyright

© Perna et al; licensee Chemistry Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.