Figure 3.

Peptide-based PPI inhibitors targeting Bcl-2 Family PPIs. (A) Structural overview of the Bcl-xl/Bak peptide PPI complex (PDB ID: 1bxl). Bcl-xl and Bak are shown in gray and green, respectively. Hydrophobic residues along the PPI interface are highlighted in purple (Bcl-xl) and green (Bak peptide) stick correspondingly. (B) Development scheme of Terephthalamide derivatives as BH3 mimetics peptide PPI inhibitors. (C) Binding interactions between Biphenyl-cross-linked Noxa peptide (blue carbon atoms) and Mcl-1 (gray carbon atoms). The key residues of side chains in Mcl-1 are labeled in yellow. The red dashed lines represent the hydrogen bonds between Biphenyl-cross-linked Noxa peptide and Mcl-1. (D) Development scheme of Noxa stapled peptides as Mcl-1 inhibitors.