Submission Details
Molecule(s):
Cn1cc(CCCc2ccccc2)c(C(=O)NC[C@@H]2CCCO2)n1
Cn1cc2c(n1)C(=O)N(C[C@@H]1CCCO1)CN2
Cn1cc2c(n1)C(=O)N(C[C@@H]1CCCO1)CN2CCc1ccccc1
CC(C)CC(NC1CC[C@@H](CNC(=O)c2ccn(C)n2)O1)C(=O)NC(C(=O)NC(Cc1ccccc1)C(=O)NC(CCC(N)=O)C(=O)O)[C@@H](C)O
CC(C)CC(NC1CC[C@@H](CNC(=O)c2ccn(C)n2)O1)C(=O)NC(C(=O)NC(Cc1ccccc1)C(=O)O)[C@@H](C)O
CC(C)CC(COC[C@H]1CC[C@@H](CNC(=O)c2ccn(C)n2)O1)C(=O)NC(C(=O)NC(Cc1ccccc1)C(=O)NC(CCC(N)=O)C(=O)O)[C@@H](C)O
CC(C)CC(COC[C@H]1CC[C@@H](CNC(=O)c2ccn(C)n2)O1)C(=O)NC(C(=O)NC(Cc1ccccc1)C(=O)O)[C@@H](C)O
Design Rationale:
By eye followed by docking. Based on x1187 bound at deep site on dimer interface and merging with amino acids 302-306. Pocket is present in apo structure where DMSO is also bound. Binding of fragment causes movement/disordering of the C-terminal residues 301-306 which form part of the dimer interface. Interfering with formation of dimer may affect substrate binding. Fragment x1187 can either be merged with residues 302-306 or grown into the binding pocket of Phe305. X1187 would also lend itself to simple amide coupling chemistry to quickly produce a small library to explore the relevance of this pocket.