Magali Zundel

Inhibition of lipases by phosphonates

Ethyl hexylchlorophosphonate and analogues thereof were investigated as inhibitors of lipases. Both microbial and mammalian lipases were irreversibly inhibited. The inhibition could be monitored by p-nitrophenol release from the corresponding ethyl p-nitrophenyl hexylphosphonate inhibitor. Quantitative analysis of the data indicated that a 1:1 lipase-inhibitor complex was formed during inhibition. Enantioselective inhibition was found for the lipases derived from Candida antarctica and Rhizomucor miehei using pure enantiomers of ethyl p-nitrophenyl hexylphosphonate as inhibitors. Using the same inhibitor, reversed enantioselectivity was found for the protease alpha-chymotrypsin as compared to the two lipases.