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.
Novo Nordisk A/S, Bagsvaerd, Denmark.
F
F
Björkling
A
A
Dahl
S
S
Patkar
M
M
Zundel
D000818:Animals; D001665:Binding Sites; D002417:Cattle; D004950:Esterases / Q000037:antagonists & inhibitors; D005658:Fungi / Q000201:enzymology; D006168:Guinea Pigs; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D008049:Lipase / Q000037:antagonists & inhibitors*; D008099:Liver / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D008433:Mathematics; D015394:Molecular Structure; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010179:Pancreas / Q000201:enzymology; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013552:Swine
D007202:Indicators and Reagents; D009943:Organophosphorus Compounds; D011480:Protease Inhibitors; D004950:Esterases; D008049:Lipase