FIGURE 2.

RO-57-BpB targets the PS N-terminal fragment. A, structures of RO-57 and its photoaffinity labeling derivative RO-57-BpB. B, dose-response analysis of γ-secretase activity modulation by RO-57 and RO-57-BpB in HEK293/sw cells by Aβ sandwich immunoassay. Data are represented as mean ± S.E. (n = 3). Note that for most data points, error bars are too small to be displayed. C, specific labeling by photoactivated RO-57-BpB of the PS1 and PS2 NTFs but not the other γ-secretase subunits as detected by immunoblot analysis. Quantitation of PS NTF binding is shown in the right panel. Data are represented as mean ± S.E. (n = 5). NCT, nicastrin. D, the absence of APP CTF labeling by RO-57-BpB as detected by immunoblot analysis.