INHIBITION OF MICROBIAL LIPASES WITH STEREOISOMERIC TRIRADYLGLYCEROL ANALOG PHOSPHONATES

1,2(2,3)-Diradylglycero O-(p-nitrophenyl) n-hexylphosphonates were syn thesized, with the diradylglycerol moiety being di-O-octylglycerol, 1- O-hexadecyl-2-O-pyrenedecanylglycerol, or 1-O-octyl-2-oleoyl-glycerol, and tested for their ability to inactivate lipases from Chromobacteri um viscosum (CVL) and Rhizopus oryzae (ROL). The experimental data ind icate the formation of stable, covalent 1:1 enzyme-inhibitor adducts w ith the di-O-alkylglycero phosphonates. The differences in reactivity of diastereomeric phosphonates with opposite configuration at the glyc erol backbone was less expressed with both enzymes tested as compared to the influence of the stereochemistry at the phosphorus. Both lipase s exhibited the same preference for the chirality at the phosphorus th at was independent from the absolute configuration at the glycerol bac kbone. However, with CVL and ROL the inhibitors with the active site s erine-directed phosphonate linked at position sn-1 of the glycerol moi ety reacted significantly faster than the corresponding sn-3 analogs, reflecting the sn-1 stereopreference of the enzymes towards triacylgly cerol analogs with a sn-2 O-alkyl substituent. In contrast, the phosph onates based on the 1-O-octyl-2-oleoylglycerol did not significantly i nactivate CVL. Unexpectedly, these substances were hydrolyzed in the p resence of lipase.