Origin of rate-acceleration in ester hydrolysis with metalloprotease mimics.
Mimics of carboxypeptidase A, a prototypical metalloprotease, were synthesized by linking macrocyclicpolyamines to the primary side of beta-cyclodextrin followed by complexing with Zn(II). These enzyme mimics exhibit saturation kinetics in hydrolysis of p-nitrophenyl acetate (PNPA) and enhance the rate of hydrolysis reaction by almost 300-fold. The effective molarities (EM) of the mimics range from 0.2 to 1.9 M. Origin of the rate acceleration was examined: the reactivity of Zn(II) complexes of [12]aneN3 [12]aneN4, and [14]aneN4 for hydrolyzing PNPA increases with increase in basicity of the zinc bound hydroxides [Zn(II)-OH], yielding a linear Brönsted plot. Free hydroxide fits well on this plot. A similar plot was obtained with the enzyme mimics. The Brönsted relationships indicate that the Zn(II)-OH in the catalytic systems hydrolyzes the ester by direct nucleophilic attack on the ester carbonyl of cyclodextrin-bound but not Zn(II)-coordinated PNPA.
Kim
D H
DH
Center for Biofunctional Molecules and Department of Chemistry, Pohang University of Science and Technology, South Korea. dhkim@vision.postech.ac.kr
Lee
S S
SS
D001665:Binding Sites; D002268:Carboxypeptidases / Q000138:chemical synthesis / Q000378:metabolism; D002384:Catalysis; D003505:Cyclodextrins / Q000737:chemistry; D004952:Esters / Q000378:metabolism*; D006868:Hydrolysis; D007700:Kinetics; D008666:Metalloendopeptidases / Q000138:chemical synthesis* / Q000378:metabolism*; D008956:Models, Chemical; D008958:Models, Molecular; D018716:Molecular Mimicry; D015394:Molecular Structure; D009596:Nitrophenols / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism; D015032:Zinc / Q000737:chemistry; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D004952:Esters; D009596:Nitrophenols; D011073:Polyamines; D047392:beta-Cyclodextrins; C008642:4-nitrophenyl acetate; D002268:Carboxypeptidases; D008666:Metalloendopeptidases; D015032:Zinc; C031215:betadex