Why are transition state analogs good inhibitors?

Answer 1

Enzymes are thought to function primarily by stabilizing the transition state of the reaction. By binding the transition state more tightly than either the substrates or the products, the enzyme lowers the energy barrier of the reaction. Thus a transition state analog will bind more tightly to the enzyme than either the substrates or the products, preventing them from binding to the enzyme and reacting.

Answer 2

Transition state analogs closely resemble the transition state of a reaction, allowing them to bind tightly to the enzyme active site. This strong binding affinity leads to effective inhibition of the enzyme's activity. Additionally, transition state analogs can be designed to specifically target certain enzymes, making them selective inhibitors with potentially lower off-target effects.

Answer 3

Because transition states are inherently unstable, molecules resembling transition states are also likely to be unstable, and thus difficult to synthesize.