Submission Details
Molecule(s):
CS(=O)(=O)CO[C@@]1(C(=O)Nc2cncc3ccccc23)CCOc2ccc(Cl)cc21
CN(C)S(=O)(=O)CO[C@@]1(C(=O)Nc2cncc3ccccc23)CCOc2ccc(Cl)cc21
COCCO[C@@]1(C(=O)Nc2cncc3ccccc23)CCOc2ccc(Cl)cc21
O=C(Nc1cncc2ccccc12)[C@]1(OCCOC2CC2)CCOc2ccc(Cl)cc21
Design Rationale:
The designs elaborate the methyl of PET-UNK-29afea89-2 with the aim of making productive contact with the relatively non-polar S1' subsite while controlling lipophilicity. One of the sulfonyl oxygens in each of the first two designs appears to be able to accept a hydrogen bond from the side chain of N142.
Other Notes:
The A-chain of the P0157 crystal structure (ligand: PET-UNK-29afea89-2) was used for modeling and the side chain of N142 has been rotated by 180 degrees to assess potential hydrogen bond donation to the sulfonyl oxygens of the first two designs. The pdb file associated with this submission includes (1) Protein structure and its crystallographic ligand from A-chain of P0157 (2) Crystallographic ligand (MAT-POS-de59a476-4) from B-chain of aligned P0187 crystal structure (3) Binding mode generated for PET-UNK-29afea89-2 according to protocol for current submission (4) Binding modes generated for designs from PET-UNK-824b5c6a submission according to protocol for current submission (5) Binding modes generated for designs in current submission.