Compound 9 is a reversible inhibitor of a human galactosidase, a hydrolytic enzyme which hydrolyses the galactosidic linkage in compound 5 and generates galactose 6 and and hexanol 7. The transition state for this enzymatic reaction has been calculated to resemble 8.
a) Provide a rational why 9 is a potent reversible inhibitor for this enzyme (5 marks) ?
b) Using the calculated transition state 8 for this enzyme, design two potent enzyme transition state inhibitors and rationalize your design strategy (10 marks).
A) In reversible inhibition an enzyme is not permanently inhibited or damaged. The inhibition can be reversed when the inhibitor is removed. There are two different types of reversible inhibition: Competitive inhibition: in competitive inhibition the inhibitor is very similar in shape to the normal substrate.
B) Enzymes are biological catalysts. Catalysts lower the activation energy for reactions. The lower the activation energy for a reaction, the faster the rate. Thus enzymes speed up reactions by lowering activation energy.