Virtual Screening of Peptide and Peptidomimetic Fragments Targeted to Inhibit Bacterial Dithiol Oxidase DsbA
Fig 5
Compound 10 demonstrated weak inhibitory activity.
A. Differential scanning fluorimetry profile with increasing concentrations of compound 10. Similar to all other compounds tested, there was no significant shift in the unfolding temperature of EcDsbA up to 2 mM of compound 10. B. ITC profile of EcDsbA titration by compound 10, which shows no detectable binding under the conditions used (see methods for details). A similar outcome was found for the other 9 compounds. C. Compound 10 was the only one of the ten tested peptidomimetics that exhibited detectable activity in the DsbA assay, inducing a reduction in DsbA folding activity. D. Plotting the log of the peptidomimetic concentration against the rate of fluorescence increase measured in the enzyme assay allowed fitting of a sigmoidal curve and an estimated IC50 value of ~1 mM for compound 10. The positive control with no compound is shown as a white circle.