Figure 5.

Representative transition-state analog inhibitors (TSAs) and affinity labeling reagents for γ-secretase. Functional groups that mimic the transition state of aspartyl protease catalysis are highlighted in red. Reactive groups leading to covalent attachment are blue, and linker-biotin moieties are in green. Boxed is the general structure of the tetrahedral intermediate formed upon addition of water to the scissile amide bond during aspartyl protease catalysis. Residues P1, P2, P3 and P1′, P2′, P3′ relative to the scissile amide bond are indicated.