Submission Details

Design Rationale:

This molecule was specifically created to have the S-end bind as closely as possible to the area around Cysteine 154, in order to form S-S bonds, and the aromatic ring in another part of the active site where other inhibitors can be found. Chimera helped identify Histidine 164 and Asparagine 28 as neighboring aminoacids that could form H-bonds with the inhibitor - hence why the -NH2 and -OH groups exist. The carbon between -OH and the 6-membered ring was added because of the relative positions of Asparagine 28 and Histidine 164, in order to make the -OH more accessible for H-bonding. The double bonds ensure that the S-end stays in place and docks exactly as planned. The aromatic ring with the two N atoms stems from MxPro-0354, which was the inspiration for this molecule.

Other Notes:

This molecule is fully within Lipinski's rule of five, with 4 H-bond donors, 3 H-bond acceptors, a molecular weight of 247.32 Da, and LogP of 1.38. Docking with SwissDock resulted in the molecule having a G = -6.64 kcal/mol when docked at Cysteine 154.