Question

Catalytic antibodies catalyze a reaction by forcing the conformation of the substrate in the direction of the transition state. The synthesis of antibody is carried out in the presence of a transition state analog-a stable molecule that structurally resembles the transition state. This causes an antibody to be generated that recognizes and binds to the transition state, thereby stabilizing it. For example, the following transition state analog has been used to generate a catalytic antibody that catalyzes the hydrolysis of structurally similar ester:

a. Draw a possible transition state for the hydrolysis of the reaction.

b. The following transition state analog is used to generate a catalytic antibody for the catalysis of ester hydrolysis. Draw the structure of an ester whose rate of hydrolysis would be increased by this catalytic antibody.

c. Design a transition state analog that catalyzes amide hydrolysis at the amide group indicated.

Short answer

a.

b.

c.

Step-by-step solution

Step-by-Step SolutionStep 1: Finding transition state for the hydrolysis reaction

a.

Transition state

This is the transition state when the tetrahedral intermediate formation is rate-limiting.

b.

Transition state (Collapsing)

This is the transition state when the tetrahedral intermediate collapse is rate limiting.When tetrahedral intermediate is formed, it collapses and the carbonyl group is produced again. The leaving group gets ejected in elimination reaction.

Structure of the ester

Structure of ester

This is the structure of the ester whose hydrolysis rate is increased by this catalytic antibody.

Transition state analog designing

Transition state analog

This is the transition state analog. This is formed by doing amide hydrolysis which occurs at the amide group.