Figure 8.

Functional probes for γ-secretase. Peptides based on the TMD of APP were designed with helix-inducing α-aminoisobutyric acid (Aib) installed in the N-terminal region. Proteolytic products were detected by LC-MS. Endoproteolytic (ε) sites, indicated by the arrowheads below the peptide sequence, were determined by analysis of AICD-like products. Trimming sites, indicated by the arrows above the peptide sequence, were determined by analysis of Aβ-like products. Note that replacement of the most C-terminal Aib in peptides 19–21 with the corresponding APP TMD residue (peptides 22–24) leads to most effective trimming, producing shorter Aβ-like products.