Submission Details

Design Rationale:

The objective of the design is to assess the benefits of linking warheads that can reversibly form covalent bonds with the catalytic cysteine to the fragment-derived inhibitor X_2646. The two selected warheads would be expected to provide a good range of 'warhead affinity' for cysteine proteases such as cathepsins and cruzain. Having IC50 values for these two compounds could inform predictions for other warheads such α-ketoamides. The binding modes have been generated by manual manipulation of the model of the bound X_2646 ligand. I have uploaded some notes to figshare and a PDB file with potential binding modes can also be downloaded: https://doi.org/10.6084/m9.figshare.12440486.v1