Endothiopeptide inhibitors of HIV-1 protease

Endothiopeptide inhibitors of HIV-1 protease were synthesized by chemical and enzymatic methods to individually replace each backbone amide bond in 1 with a thioamide-linkage. Interestingly, agent 7, which contains a thioamide-linkage between the P2′ and P3′ positions of 1, was the most potent, competitive inhibitor of HIV-1 protease with a Ki of 3.4 μM.