Fig. 1: Design of macrocycle-based PROTACs with high affinity for cyclophilins.
From: Macrocycle-based PROTACs selectively degrade cyclophilin A and inhibit HIV-1 and HCV
a X-ray crystal structure of sanglifehrin A-CypA complex (PDB 1YND) (left) and TWH106 docked into CypA (right). The TWH106 nitrophenyl moiety fills a subpocket near residues K82 and E81 and the nitro group H-bonds with K82 (arginine in CypB). Two solvent-exposed methyl groups ✱ and # of TWH106 were used to synthetically grow PROTACs. b Chemical structure of our two TWH106-based PROTACs CG167 and RJS308.
