Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

268 Chapter 12
HO
O
HO
OH
HO OH
O
OH OH
OH
OH
O
6
O
AcO
3300-fold accelerated
base-catalysed hydrolysis of
HO
O
Figure 12.15 Cyclodextrin-catalysed ester hydrolysis.
Functionalisation of the free hydroxyl groups on the rim of the cavity opens
up new possibilities for the design of enzyme models. One example is the
cyclodextrin shown in Figure 12.16, functionalised with two imidazole side
chains. This derivative was found to catalyse the regioselective hydrolysis of a
cyclic phosphodiester substrate, with a rate constant of 3 10 4 s 1 . The pH/
rate proWle of this catalyst showed that maximum activity was obtained at pH
6.3, at which point one of the imidazole groups is protonated and the other
deprotonated. The proposed mechanism shown in Figure 12.16 involves bifunc-
N
NH
HN
N
catalyses phosphate ester hydrolysis:
O
O
P O −
O
OH
OPO 3
2−
v max 3 10 −4 s −1
N
N
H
O O −
O P O
O H
H
N
N
walls of cyclodextrin`
Figure 12.16 Functionalised cyclodextrin model of ribonuclease A.