TY - JOUR
T1 - Halo enol lactone inhibitors of chymotrypsin
T2 - Burst kinetics and enantioselectivity of inactivation
AU - Baek, Du Jong
AU - Katzenellenbogen, John A.
PY - 1991/8/15
Y1 - 1991/8/15
N2 - Burst kinetics in the inactivation of α-chymotrypsin by halo enol lactones 1 and 2 was observed. These results are consistent with a kinetic scheme that includes partitioning of the first acyl enzyme between transient inhibition and permanent inactivation. Partition ratios were estimated from the measured rates of the irreversible inactivation and the rates of deacylation of the second acyl enzyme. Halo enol lactones with a large burst resulted in small partition ratios, indicating a high potency of inactivation. We also observed enantioselectivity in the burst of inactivation such that the R enantiomer of lactone 1 showed a large burst, while the S enantiomer showed a little burst. This suggests that it is the R enantiomer whose binding is better suited for the covalent derivatization of the enzyme, or whose reactive halomethyl group is in an unfavorable position for the hydrolysis by water.
AB - Burst kinetics in the inactivation of α-chymotrypsin by halo enol lactones 1 and 2 was observed. These results are consistent with a kinetic scheme that includes partitioning of the first acyl enzyme between transient inhibition and permanent inactivation. Partition ratios were estimated from the measured rates of the irreversible inactivation and the rates of deacylation of the second acyl enzyme. Halo enol lactones with a large burst resulted in small partition ratios, indicating a high potency of inactivation. We also observed enantioselectivity in the burst of inactivation such that the R enantiomer of lactone 1 showed a large burst, while the S enantiomer showed a little burst. This suggests that it is the R enantiomer whose binding is better suited for the covalent derivatization of the enzyme, or whose reactive halomethyl group is in an unfavorable position for the hydrolysis by water.
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U2 - 10.1016/0006-291X(91)91040-J
DO - 10.1016/0006-291X(91)91040-J
M3 - Article
C2 - 1872851
AN - SCOPUS:0026069901
VL - 178
SP - 1335
EP - 1342
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -