Beilstein J. Org. Chem.2016,12, 2784–2792, doi:10.3762/bjoc.12.277
for the development of customized PqsD inhibitors as well as a chemical toolbox to investigate the activity and active site specificity of the enzyme.
Keywords: activity-basedprobes; PqsD; protein labelling; Pseudomonas aeruginosa; quinolones; Introduction
The emergence of multi-drug resistant
which could allow to study its active site reactivity in greater detail and apply a competitive labelling platform to discover potential PqsD inhibitors.
Results and Discussion
Electrophilic activity-basedprobes
The primary structure of PqsD comprises in total six cysteines. However, only one of them
underlining the selectivity of our probes (Figure 3C). These results indicate that probes CA1–3 are specific and covalently bind to Cys112 of PqsD and are thus, to the best of our knowledge, the first account of activity-basedprobes targeting and selectively labelling the active site of PqsD.
Interestingly
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Graphical Abstract
Figure 1:
Quinolone signals of Pseudomonas aeruginosa. A) Structures of HHQ and PQS. B) Proposed mechanism fo...
Beilstein J. Org. Chem.2013,9, 15–25, doi:10.3762/bjoc.9.3
of this new class of inhibitors.
Keywords: activity-basedprobes; Chagas’ disease; cruzain; CYP51; 14-α-demethylase; hybrid drugs; Trypanosoma cruzi; Introduction
The kinetoplastid protozoan Trypanosoma cruzi is the causative agent of Chagas’ disease, a leading cause of heart failure in endemic
the use of cell-based counter assays that can detect action at specific targets or signaling pathways of interest. Activity-basedprobes can serve as useful tools to verify on-target action during the course of chemical optimization campaigns.
Chemical structures of vinylsulfone-based cruzain
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Graphical Abstract
Figure 1:
Chemical structures of vinylsulfone-based cruzain inhibitors 1–4, known TcCYP51 inhibitor 5, dihydr...