The reaction of organophosphorus compounds with hydrolytic enzymes - III. The inhibition of chymotrypsin and trypsin
article
Reaction rate constants were determined for the inhibition reaction of chymotrypsin and trypsin by a number of organophosphorus compounds of the general formula R1R2P(O)X at pH 7·7 and 25°. In all cases the rate constants for the inhibition of chymotrypsin were greater than the corresponding rate constants for the inhibition of trypsin. In the two series investigated there is a correlation between the rate of enzyme inhibition and the strength of the PX bond as expressed by alkaline hydrolysis and pKa values of HX. The influence of the structure of the groups R1 and R2 on the rate of enzyme inhibition does not parallel the reactivity measured as alkaline hydrolysis. Cycloalkyi methylphosphonofluoridates proved to be the most active inhibitors investigated for both enzymes. The influence of the temperature on the reaction rate has been investigated in five cases. It seems that the rapid reaction of the compounds with the enzymes, compared with alkaline hydrolysis, is caused by a lowering of the activation enthalpy rather than by an increase of the activation entropy. Chymotrypsin shows marked stereospecificity in a number of cases. The enzyme reacted more than a hundred times faster with one of the stereoisomers of pinacolyl methylphosphonofluoridate than with its optical antipode. A calculation method for the determination of the rate constants of the stereoisomers from the data obtained with the racemic compound is given in an appendix. © 1966.
Topics
TNO Identifier
226926
ISSN
00062952
Source
Biochemical Pharmacology, 15(9), pp. 1361-1377.
Pages
1361-1377
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