Figure 4.

(a) Superimposition of 22 (red, PDB ID 5jm4) and selected phosphorylated peptides (blue, PDB IDs iqja, 1ywt, 2bn5, 2btp, 2c74, 2npm, 2v7d, 3e6y, and 3nkx) bound to 14–3–3. Peptide backbones are shown as ribbons and important side chains explicitly. (b) FP competition using labeled Raf-peptide as tracer (10 nM with 2 μM 14–3–3) and nonlabeled versions of 1, 2, and 22 (including their IC₅₀ values). (c) Inhibition of MMP1 transcription in a cell-based assay after pathway activation with 14–3–3ζ (c = 200 nM). Cells were treated for 24 h in the absence and presence of 1, 2, or 22 (20 μM). Expression levels of mRNA were measured by quantitative real time PCR (for details, see Supporting Information).