Figure 1.
Synthesis, sequence, and biochemical analysis of SAH-p53 peptides. (A) Non-natural amino acids were synthesized as described and cross-linked by ruthenium-catalyzed ring-closing olefin metathesis. (B) SAH-p53 compounds were generated by stapling the p5314-29 sequence at the indicated positions. Charge, α-helicity, hDM2 binding affinity, cell permeability, and impact on cell viability are indicated for each compound. (C, E) Circular dichroism spectra revealed enhancement of α-helicity for SAH-p53 compounds. (D, F) Fluorescence polarization assays using FITC-peptides and hDM217-125 demonstrated subnanomolar hDM2-binding affinities for select SAH-p53 peptides. Note: UAH-p53-8 is the “unstapled” form of SAH-p53-8.