Rational design of alpha-keto triglyceride analogues as inhibitors for Staphylococcus hyicus lipase

A series of alpha-keto triglyceride analogues that inhibit the lipase of Staphylococcus hyicus has been synthesized. Nonhydrolyzable ether, carbamoyl or amide bonds were used in replacing ester bonds to forestall hydrolysis at positions 1 and 2. An alpha-keto fatty acid was also introduced at position 3 which may have inhibited the lipase. It was observed that an ester or a hydroxyl on position 3 had no effect on the lipase. The analogues react with the active site Ser of the lipase and copy the tetrahedral intermediate involved in substrate hydrolysis.