Figure 1. Broad-spectrum BCL-2 family binding activity of a stapled BIM BH3 helix.
(A) Sequence composition of BIM SAHBA and its R153D mutant. “X” denotes the position of the nonnatural amino acid within each peptide. (B–E) BIM SAHBA binds to a broad range of antiapoptotic targets with high affinity. R153D mutagenesis shifts the isotherms to the right, reflecting the impairment of binding activity. Data are mean ± SEM for experiments performed at least in triplicate. mP, units of millipolarization. (F and G) BIM SAHBA triggers dose-responsive BAX-mediated liposomal release, whereas the R153D mutant has no effect. The liposomal release assays were performed in triplicate with similar results.