Table 1.

Summary of Covalent Inhibition Strategies

Reversibility of Inhibition	Class of Inhibitor	Scheme	Major Selectivity Determinant
Reversible	Covalent Reversible	$\text{E+I}\rightleftharpoons \mathrm{E}\cdot \mathrm{I}\rightleftharpoons \mathrm{E}-\mathrm{I}$	Thermodynamic equilibrium
	Slow Substrate	$\text{E+I}\rightleftharpoons \mathrm{E}\cdot \mathrm{I}\to \mathrm{E}-\mathrm{I}\to \mathrm{E}+\mathrm{P}$	Enzymatic catalysis
Irreversible	Residue-Specific Reagent	$\text{E+I}\to \mathrm{E}-\mathrm{I}$	Chemical reactivity
	Affinity Label: Classical	$\text{E+I}\rightleftharpoons \mathrm{E}\cdot \mathrm{I}\to \mathrm{E}-\mathrm{I}$	Effective molarity & chemical reactivity
	Affinity label: Quiescent	$\text{E+I}\rightleftharpoons \mathrm{E}\cdot \mathrm{I}\underset{"\text{off}\text{pathway}"}{\overset{\text{catalyzed}}{\to }}\mathrm{E}-\mathrm{I}$	Effective molarity & “off pathway” cat.
	Affinity label: Photoaffinity	$\text{E+I}\rightleftharpoons \mathrm{E}\cdot \mathrm{I}\stackrel{\text{hυ}}{\to }\mathrm{E}-\mathrm{I}$	Effective molarity & light activation
	Mechanism-Based	$\text{E+I}\rightleftharpoons \mathrm{E}\cdot \mathrm{I}\underset{"\text{off}\text{pathway}"}{\overset{\text{catalyzed}}{\to }}\underset{\begin{array}{l}\downarrow \\ \text{E+P}\end{array}}{\mathrm{E}\cdot \mathrm{I}\ast }\to \mathrm{E}-\mathrm{I}$	Enzymatic catalysis