733744-92-8Relevant academic research and scientific papers
Probing pockets S2-S4′ of the γ-secretase active site with (hydroxyethyl)urea peptidomimetics
Esler, William P.,Das, Chittaranjan,Wolfe, Michael S.
, p. 1935 - 1938 (2007/10/03)
(Hydroxyethyl)urea peptidomimetics are potent inhibitors of γ-secretase that are accessible in a few synthetic steps. Systematic alteration of P2-P4′ revealed that the corresponding S2-S4′ active site pockets accommodate a variety of substituents, consistent with the fact that this protease cleaves a variety of single-pass membrane proteins; however, phenylalanine is not well tolerated at P2′. A compound spanning P2-P3′ was identified as a low nM inhibitor of γ-secretase activity both in cells and under cell-free conditions.
