Hauske, Patrick; Meltzer, Michael; Ottmann, Christian; Krojer, Tobias; Clausen, Tim; Ehrmann, Michael; Kaiser, Markus:
Selectivity profiling of DegP substrates and inhibitors
2009
In: Bioorganic & medicinal chemistry : a Tetrahedron publication for the rapid dissemination of full original research papers and critical reviews on biomolecular chemistry, medicinal chemistry and related disciplines, Jg. 17 (2009), Heft 7, S. 2920 - 2924
Artikel/Aufsatz in Zeitschrift / Fach: Biologie
Fakultät für Biologie
Titel:
Selectivity profiling of DegP substrates and inhibitors
Autor(in):
Hauske, Patrick im Online-Personal- und -Vorlesungsverzeichnis LSF anzeigen; Meltzer, Michael im Online-Personal- und -Vorlesungsverzeichnis LSF anzeigen; Ottmann, Christian; Krojer, Tobias; Clausen, Tim; Ehrmann, Michael im Online-Personal- und -Vorlesungsverzeichnis LSF anzeigen; Kaiser, Markus im Online-Personal- und -Vorlesungsverzeichnis LSF anzeigen
Erscheinungsjahr:
2009
Erschienen in:
Bioorganic & medicinal chemistry : a Tetrahedron publication for the rapid dissemination of full original research papers and critical reviews on biomolecular chemistry, medicinal chemistry and related disciplines, Jg. 17 (2009), Heft 7, S. 2920 - 2924
ISSN:

Abstract:

Protein quality control factors are involved in many key physiological processes and severe human diseases that are based on misfolding or amyloid formation. Prokaryotic representatives are often virulence factors of pathogenic bacteria. Therefore, protein quality control factors represent a novel class of drug targets. The bacterial serine protease DegP, belonging to the widely conserved family of HtrA proteases, exhibits unusual structural and functional plasticity that could be exploited by small molecule modulators. However, only one weak synthetic peptide substrate and no inhibitors are available to date. We report the identification of a potent heptameric pNA-substrate and chloromethyl ketone based inhibitors of DegP. In addition, specificity profiling resulted in the identification of one strong inhibitor and a potent substrate for subtilisin as well as a number of specific elastase substrates and inhibitors. Graphical abstract