Format

Send to

Choose Destination
Bioorg Med Chem. 2009 Apr 1;17(7):2920-4. doi: 10.1016/j.bmc.2009.01.073. Epub 2009 Feb 5.

Selectivity profiling of DegP substrates and inhibitors.

Author information

1
Chemical Genomics Centre der Max-Planck-Gesellschaft, Otto-Hahn-Str. 15, D-44227 Dortmund, Germany.

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.

PMID:
19233659
DOI:
10.1016/j.bmc.2009.01.073
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center