| Assay Method Information | |
| | Identification of NDM-1 Inhibitors and their Biochemical Activities |
| Description: | All NDM-1 β-lactamase hit molecules were identified from the qDOS38_2 library. As previously noted, NDM-1 is a class B metallo-β-lactamase with a different structure and active site chemistry compared to OXA-48. Nevertheless, it also contains a binding pocket for the β-lactam carboxylate group. Many of the compounds enriched by affinity selection against NDM-1 contained the designed carboxylic acid in the form of salicylic acid. Without wishing to be bound by any theory, salicylic acids are known to chelate metal ions, suggesting these compounds utilize active site zinc for binding affinity. A total of three highly-enriched compounds were re-synthesized in the absence of the DNA barcode and tested for inhibition using an NDM-1 assay with imipenem as the reporter substrate. The assay buffer also contained 10 M of zinc ions as required for NDM-1 activity. CDD-2350 and CDD-2373 were weak inhibitors with their Ki values greater than 100 μM. In contrast, CDD-2376 was more potent, with a Ki of 3.3 μM. |
| Affinity data for this assay | |
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